Appendix 1 – Transmission Electron Microscopy in Virology: Principles, Preparation Methods and Rapid Diagnosis

Hans R. Gelderblom

Formerly, well-equipped virology institutes possessed many different cell culture types, various ultracentrifuges and even an electron microscope. Tempi passati? Indeed! Meanwhile, molecular biological methods such as polymerase chain reac- tion, ELISA and chip technologies—all fast, highly sensitive detection systems— qualify the merits of electron microscopy within the spectrum of virological methods. Unlike in the material sciences, a significant decline in the use of electron microscopy occurred in life sciences owing to high acquisition costs and lack of experienced personnel. Another reason is the misconception that the use of electron microscopes is expensive and time consuming. However, this does not apply to most conventional methods. The cost of an electron-microscopic preparation, the cost of reagents, contrast and embedding media and the cost of carrier networks are low. Electron microscopy is fast, and for negative staining needs barely 15 min from the start of sample preparation to analysis. Another advantage is that a virtually unlimited number of different samples can be analysed—from nanoparticles to fetid diarrhoea samples.

A.1 Principles of Electron Microscopy and Morphological Virus Diagnosis

In transmission electron microscopy, accelerated, monochromatic electrons are used to irradiate the object to be imaged. This leads to interactions: the beam electrons are scattered differentially by atomic nuclei and electron shells, losing some of their energy. After magnification through a multistage lens system, a 1,000-fold higher resolution is obtained with a transmission electron microscope than with a light microscope (2 nm vs. 2 mm) owing to the much shorter wavelength of electrons in comparison with visible light. Hence, in contrast to light microscopy, transmission electron microscopy is capable of visualizing even the smallest viruses. Scanning electron microscopy depicts surfaces, but no internal structures. Even though confocal laser scanning light microscopy can localize individual viruses, the fluorescence signal does not image the particle. However, identification

S. Modrow et al., Molecular Virology, DOI 10.1007/978-3-642-20718-1, 949 # Springer-Verlag Berlin Heidelberg 2013 950 H.R. Gelderblom of viruses and description of virus–cell interactions frequently require structural information in high resolution, as can be supplied only by electron microscopy. Electron microscopes are also used in the diagnosis of viral diseases: although a modern diagnostic laboratory allows high sample throughput, it requires a clinical diagnosis and pathogen-specific reagents. By contrast, electron microscopy “illu- minates,” after rapid and simple contrasting, and provides a high-resolution “open view” of the finest structures in a sample. Thereby, every pathogen is rendered visible also in the case of multiple infections or unknown pathogens, or agents that have never been considered by the clinician, and even genetically engineered organisms. Infectious agents exhibit constant morphological characteristics such as size, shape, subunits, perhaps an envelope, surface projections or protrusions and specific nature of the interaction with the host cell. These criteria help to assign the object in question to a specific pathogen family. Although the morphological diagnosis “viruses of the herpesvirus family” does not indicate the viral species, as a “family diagnosis” it gives the clinician or epidemiologist—along with the previous clinical history—a rapid perspective on the action required, e.g. antiviral therapy, quarantine or vaccination. If the pathogen family is ascertained, if neces- sary, even a “fine diagnosis” by molecular methods or by immune electron micros- copy can be significantly accelerated. Independence from pathogen-specific reagents is a great advantage for diagnosis of infections, epidemics and bioterrorism hazards, but also in the characterization of laboratory products and biological preparations, vaccines, therapeutic antibodies and in the frequently neglected internal quality assurance. A disadvantage of electron microscopy is that it has a very narrow field of view, owing to the very high magnification; therefore, high particle concentrations are required for detection (more than 105 particles per millilitre). Samples with particle concentrations below this threshold need to be effectively and rapidly enriched before use. Furthermore, electron microscopy does not allow high-throughput analyses. The examiner must be concerned only with one preparation for at least 20 min before it can classify it as “negative.”

A.2 Transmission Electron Microscopy: Thin Preparations Are Required

In preparations with a layer thickness of more than 80 nm, the imaging electrons are scattered several times; the consequences are loss of image sharpness and informa- tion. The necessary thinner specimens are obtained after embedding the samples in resin (Epon) in ultrathin sections or by negative staining of particle suspensions. Both methods result de facto in a resolution of 2 nm. Viruses are biological macromolecules which consist essentially of light atoms with low mass density. In the transmission electron microscope, they appear highly transparent and with low contrast. Detailed and contrast-rich images can be obtained by absorption and scattering of electrons only at high mass density of the objects, as can be created by negative or positive staining (Fig. A.1). Appendix 1 – Transmission Electron Microscopy in Virology 951

Fig. A.1 Preparation for transmission electron microscopy (TEM). Principle of ultrathin-section and negative-contrast TEM using the example of a herpesvirus. The upper half shows the ultrathin section of a specimen embedded in Epon. For this purpose, in vitro infected cells were fixed with glutaraldehyde, incubated with heavy metal salts, dehydrated and finally embedded in resin. The hardened samples were cut in an ultramicrotome into 50-nm-thick specimens, treated again with contrast medium and analysed by TEM. The following viral structures can be recognized from outside to inside: the viral envelope as a lipid bilayer with glycoprotein protrusions, a moderately contrasted tegument, the hexagonal viral capsid and deep inside the viral DNA complex. Heavy metal salts are also used as contrast media in negative staining (lower half) (see Fig. A.2). In this case, the short exposure leads only slightly to chemical bonds. The viral components are trans- parent, they appear bright, negatively contrasted against the dark, electron-dense contrast medium, and we can recognize the fragile envelope of a herpesvirus with its glycoprotein processes and inside the contrast-medium-filled capsid with capsomeres and a typical diameter of 100 nm

Negative staining requires particle suspensions, as they can be directly prepared from swab samples from patients, cell culture supernatants, disrupted cells, pulver- ized tumours, urine, serum or stool samples, bacterial colonies and bioterrorism- suspected “powder.” In principle, any organic or inorganic material is suitable if it can be resuspended. Rough cell debris is removed by low-speed centrifugation. The sample is then stained (Fig. A.2). Usually, a copper grid (carrier network) is placed on a drop of the suspension. The grid carries a stable and very electron transparent plastic carrier film with regularly dispersed holes. After short 952 H.R. Gelderblom

Fig. A.2 Negative staining procedure. Drops of the suspension to be examined, washer fluid and contrast medium are applied from left to right in a horizontal row on an inert surface. Grids (in the Petri dish) are placed on the sample using a pair of tweezers for 10 s or longer, are then washed with drops of double distilled water and are finally stained with contrast medium for 10 s. After excess contrast medium has been removed and subsequent air drying, the grids are well prepared for TEM. (From Gelderblom 2003) adsorption, the sample excess and interfering ions are removed with filter paper and the grid with the adsorbed material is placed for a few seconds on the contrast medium, which consists of a 0.5–4.0 % heavy metal salt solution with high mass density, such as phosphotungstic acid or uranyl acetate. Excess contrast medium is removed from the “contrasted” grid, briefly air-dried and is then prepared for electron-microscopic examination. The dried, electron-dense contrast medium coats the “transparent” structures on the carrier network and renders visible surface details with very high resolution—comparable to the X-ray contrast technique. However, it can also penetrate into labile samples, facilitating the representation of internal structures. Advantageous for a natural image is that viruses, like other unstable biostructures, are closely enveloped, and thus are stabilized by the contrast medium. Thin specimens make possible, apart from negative staining, also the more complex ultrathin-section technique. For this purpose, small blocks of solid tissues, cell culture conglomerates or ultracentrifuge sediments (edge length under 1 mm) are chemically fixed by aldehydes, and incubated with heavy metal salt solutions (osmium, uranium, lead). The heavy metal salts bind to different groups in the material and this results in high mass densities and high-contrast images even of Appendix 1 – Transmission Electron Microscopy in Virology 953 internal structures, which become visible later. After dehydration, e.g. in an ascending ethanol series, the samples are embedded in resin and cut in an ultrami- crotome: sections with a thickness of 40–70 nm are restained with lead salts and analysed by electron microscopy. The entire conventional preparation requires 4–5 days. In contrast, modern, rapid methods reduce the preparation time to a few hours, but they still require considerably more effort and time than the negative staining procedure.

A.3 Perspectives for Transmission Electron Microscopy in Virology Research

When promptness, high resolution and the “open view” of electron microscopy are to be used reasonably in laboratory medicine and cell biology research, a “front- line” application is required. Therefore, this method should be used together with complementary techniques to increase its diagnostic value. An electron- microscopic laboratory should also provide more services for other institutions. Between services, routine research and basic research, there are a myriad of worthwhile tasks. Such an open-use approach should inspire the next generation of scientists, and ensure the long-term survival of electron microscopy within the life sciences.

References

Gelderblom HR (2003) Elektronenmikroskopie im Methodenspektrum der Bioterrorismus- Diagnostik. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 46:984–988

Further Reading

Biel SS, Gelderblom HR (1999) Electron microscopy of viruses. In: Cann A (ed) Virus cell culture – a practical approach, Oxford University Press, Oxford, pp 111–147 Deutsche Gesellschaft fur€ Elektronenmikroskopie (2012) DGE - work groups of the DGE. http:// www.dge-homepage.de/arbeitskreise_e.html Gelderblom HR (2001) Elektronenmikroskopische Erregerdiagnostik. BIOforum 24:105–108 Gelderblom HR (2003) Elektronenmikroskopie im Methodenspektrum der Bioterrorismus- Diagnostik. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 46:984–988 Hazelton PR, Gelderblom HR (2003) Electron microscopy for rapid diagnosis of infectious agents in emergent situations. Emerg Infect Dis 9:294–303 Kruger€ DH, Schneck P, Gelderblom HR (2000) Sixty years ago: Helmut Ruska and the visuali- zation of viruses. Lancet 355:1713–1717 Laue M, Niederwo¨hrmeier B, Bannert N (2007) Rapid diagnostic thin section electron microscopy of bacterial spores. J Microbiol Methods 70:45–54 Robert Koch Institute (2012) RKI - consultant lab for diagnostic electron microscopy in infectious diseases. http://www.rki.de/EN/Content/Institute/DepartmentsUnits/NRC/CONSULAB/ consulab_node.html

Appendix 2 – Information on the “Prototypical Electron-Microscopic Portraits” of Individual Virus Families

Hans R. Gelderblom

Poliovirus type 1 (▶ Sect. 14.1) as a prototype of the family Picornaviridae, grown in cell culture, purified by gradient centrifugation and represented by negative staining with 2 % phosphotungstic acid (PTA). Picornaviruses are isometric, have no envelope, are 28–30 nm in diameter and do not exhibit fine structures, even at high resolution. Primary magnification  60,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Human astrovirus type 1 (▶ Sect. 14.2), the prototype of the family Astroviridae (Greek aster, “star”), grown in cell culture, purified by gradient centrifugation and represented by negative staining with 1 % uranyl acetate. The isometric, non- enveloped astroviruses are 27–30 nm in diameter, and occasionally show a clear, star-shaped five- or sixfold symmetry. Primary magnification  60,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Rabbit haemorrhagic disease virus (▶ Sect. 14.3) as an example of the family Caliciviridae (Greek kalix, “chalice”); partially purified particle suspension from the liver of diseased rabbits, represented by negative staining with uranyl acetate. The isometric caliciviruses have a diameter of 28–34 nm and have capsid struc- tures, which can be used diagnostically: striking cup-shaped depressions in rabbit haemorrhagic disease virus and sapoviruses. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Hepatitis E virus (▶ Sect. 14.4), the prototype of the family Hepeviridae, prepared from the bile of a diseased patient after negative staining with PTA. The isometric particles are 27–30 nm in diameter, and aggregated in vivo by the action of the antibodies from the patient. Primary magnification  40,000, bar 100 nm. (Kindly provided by B€arbel Hauro¨der, Central Institute of the Bundeswehr Medical Service, Koblenz, Germany) West Nile virus (▶ Sect. 14.5) as a prototype of the family Flaviviridae, grown in cell culture, represented in ultrathin section. The spherical virus particles are approximately 50 nm in diameter, have short glycoprotein processes and are tightly enclosed by a lipid envelope. The dark-stained core of flavoviruses is determined by the viral nucleic acid. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany)

S. Modrow et al., Molecular Virology, DOI 10.1007/978-3-642-20718-1, 955 # Springer-Verlag Berlin Heidelberg 2013 956 H.R. Gelderblom

Sindbis virus (▶ Sect. 14.6) as a prototype of the family Togaviridae, grown in cell culture, partially purified by gradient centrifugation and negatively contrasted with uranyl acetate. The virus particles have a diameter of 60–70 nm. In the image, some viruses have been penetrated by the contrast medium; viral glycoprotein protrusions are also partially visible on the lipid envelope. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Equine arteritis virus (▶ Sect. 14.7) grown in cell culture, represented in ultrathin section as a representative of the family Arteriviridae. The virions are rounded ovoid and have a diameter of 40–60 nm, are surrounded by a lipid envelope and have a narrow electron-dense ribonucleoprotein core. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) SARS-associated coronavirus (▶ Sect. 14.8) as a prototype of the family Coronaviridae, grown in cell culture, without pre-treatment, represented after negative staining with 2 % PTA. The virion is surrounded by a lipid envelope, is 90–140 nm in diameter and has striking, club-like surface processes (20 nm, peplomers), which can be relatively easily released from the surface of the virus particle by shedding (see the virion at the top right). Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Vesicular stomatitis virus (▶ Sect. 15.1) as an example of the family Rhabdoviridae (Greek rhabdos, “rod”, “stick”, or “staff”), grown in cell culture, enriched and represented after negative staining with uranyl acetate. Animal rhab- doviruses, unlike plant rhabdoviruses, are “bullet”-shaped particles that are flat- tened at one end. They are 75 nm  190 nm and have an envelope which is studded with viral glycoprotein protrusions. The helically wrapped ribonucleoprotein core resides inside—“like a beehive.” It has a diameter of 50 nm. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Equine Borna disease virus (▶ Sect. 15.2) as a prototype of the family Bornaviridae, propagated in cell culture, represented in ultrathin section. The rotund virions are 120 nm in diameter and mature by budding at the cell surface. They are enclosed by an envelope containing glycoprotein protrusions of 7 nm in length. Occasionally, thin strings of viral ribonucleoprotein complexes are recognizable inside the virus. In addition to the 120-nm-diamter particles, the virus preparations frequently also contain smaller, subviral particles of 75 nm in diameter. Primary magnification  40,000, bar 100 nm. (Kindly provided by Kouichi Sano, Depart- ment of Microbiology and Infection Control, Osaka Medical College, Japan) Human parainfluenza virus 1 (▶ Sect. 15.3) as a prototype of the family Paramyxoviridae, depicted in ultrathin section. Paramyxoviruses are released by budding at the cell surface; they are round-polymorphic and very heterogeneous in size (90–400 nm). Their envelope is densely occupied with viral glycoproteins (HN and F proteins). Cross sections of viral ribonucleoproteins are recognizable inside the virus, beneath the envelope (diameter 18–22 nm). Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Marburg virus (▶ Sect. 14.8) representing the family Filoviridae, grown in cell culture, without pre-treatment and represented after negative staining with 2 % PTA. The virus particles are clumped with cell debris. Their envelope contains Appendix 2 – Information on the “Prototypical Electron-Microscopic Portraits” 957 glycoprotein projections; the helical ribonucleoprotein complex is located inside. The diameter of filoviruses is 80 nm; their length can differ considerably: Marburg virus is 700–800 nm long, whereas Ebola virus can reach up to 15 mm. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Lymphocytic choriomeningitis virus (▶ Sect. 16.1) representing the family Arenaviridae (Latin arenosus, “sandy”), grown in cell culture. The release of virus particles occurs by budding at the cell surface. The envelope of arenaviruses carries glycoprotein protrusions and is flexible, so the released virus particles appear pleomorphic. Arenaviruses incorporate cellular ribosomes during particle assembly, and thus exhibit typical, high-contrast inclusions. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Puumala virus (▶ Sect. 16.2), a member of the genus Hantavirus, representing the family Bunyaviridae, grown in cell culture. The image shows the ultrathin section of a virus-producing cell with accumulation of released particles. The viruses are surrounded by an envelope, and have a diameter of 80–120 nm. The ribonucleoprotein strands of their segmented genome are recognizable inside the virus particles. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin). Influenza A virus (▶ Sect. 16.3) as a prototype of the family Orthomyxoviridae. The image shows the ultrathin section of a virus-producing cell. The plump, ovoid particles are 80–120 nm in diameter and carry HA and NA glycoprotein processes. The matrix protein is located directly under the envelope as a moderately dark layer. Some of the segmented ribonucleoprotein complexes can be observed inside. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Avian infectious bursal disease virus (▶ Sect. 17.1), representing the family Birnaviridae, grown in cell culture, purified by gradient centrifugation and represented by negative staining with uranyl acetate. The isometric particles are 60 nm in diameter, possess an envelope and reveal the typical capsomere structure of their capsids. Primary magnification: Â60,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Human rotaviruses (▶ Sect. 17.2) partially purified from a stool specimen and shown by negative staining with uranyl acetate. Rotaviruses are a subfamily of the family Reoviridae; the actual reoviruses are 80 nm in diameter and thus markedly larger. Rotaviruses are 70 nm in diameter and have two isometric protein capsids that lie one above the other. They occasionally show an external, spoke-shaped zone around a large inner hub (a wheel-like structure, hence their name from the Latin rota, meaning “wheel”). For most virus particles only in the surface is revealed by the contrast medium; however, the isometric core can occasionally be seen because here uranyl acetate is infiltrated into the virion. Primary magnification  60,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Human immunodeficiency virus 1, a lentivirus as a prototype of the family Retroviridae (▶ Sect. 18.1). The image shows the ultrathin section of a virus- producing T cell with different viral maturity stages. The viruses are about 958 H.R. Gelderblom

120 nm in diameter, and have a very fragile envelope. At the bottom right is a late budding phase with only scarce interconnection of the virion to the host cell: the viral envelope is densely covered with gp120 protein processes of 9–10 nm in length. Beneath the envelope, the uncleaved Gag–Pol precursor protein and the viral RNA form a 20-nm-thick, dark layer. Their cleavage by the viral protease generates the Gag proteins of the mature virion and causes a massive morphological transformation, and the virion become infectious. Mature lentiviruses (top left) have a conical core, which always contains two molecules of the viral ribonucleoprotein. The glycoprotein projections of human immunodeficiency virus and other retrovi- ruses are lost in a time- and temperature-dependent manner: this “shedding” leads to loss of infectivity. Lentiviruses of humans and monkeys have lateral bodies consisting of the structural proteins that are not required for remodelling. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Hepatitis B virus (▶ Sect. 19.1) represented by negative staining with PTA in immune aggregates. The image shows three spherical virions with a diameter of 42–45 nm (Dane particles), which are coaggregated with a variety of non-infectious HBsAg particles (20-nm particles, Australia antigen). The virions have a tight- fitting envelope that surrounds the viral capsid (diameter 28–30 nm). The serum of a hepatitis B infected patient was used for aggregation of hepatitis B virus and HBs particles; cross-linking antibodies hide finer details. Primary magnification  60,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) BK polyomavirus (▶ Sect. 19.2), a human polyomavirus representing the family Polyomaviridae. BK polyomavirus was imaged directly from the urine of an immunosuppressive-treated patient after negative staining with uranyl acetate. The virus particles are 45 nm in diameter and have no envelope. Their isometric capsids consist of 72 pentameric capsomeres. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin) Papillomavirus (▶ Sect. 19.3) from a chicken tumour (chaffinch), representing the family Papillomaviridae. The specimen originated from a biopsy, was isolated by “rubbing” with sea sand and was directly depicted by negative staining unpurified. These enveloped virus particles are isometric, have a diameter of 55 nm and consist of 72 pentameric capsomers. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Fowl adenovirus 2 (▶ Sect. 19.4) as an example of the family Adenoviridae, highly purified by gradient centrifugation and represented by negative staining with uranyl acetate. Adenoviruses are 75–80 nm in diameter; their non-enveloped capsids clearly show their perfect icosahedral symmetry and their structure made up of capsomers, which, depending on the position in the capsid, have different properties (a total of 240 hexon and 12 penton capsomers per virion). The pentons are located at the 12 vertices of the icosahedron, and each penton base is associated with a rigid-fibre protein with a terminal knob. These fibres are anchored in poultry adenoviruses and several human adenoviruses in double form on the penton base. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Appendix 2 – Information on the “Prototypical Electron-Microscopic Portraits” 959

Equine herpesvirus 1 (▶ Sect. 19.5) from the family Herpesviridae, represented in ultrathin section. The image shows six virus particles in cross section. They are approximately 180 nm in diameter, but are in different planes, sometimes only peripherally sliced, and thus do not show all the known structural components of herpesviruses. The envelope carries a dense crown of glycoprotein processes. Below the envelope is the moderately electron-dense viral tegument layer, and further inside is the viral capsid (diameter 100 nm), which contains the highly electron-dense viral DNA genome. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Murine ectromelia virus (▶ Sect. 19.6), an orthopoxvirus as an example of the family Poxviridae, grown in cell culture and represented by negative staining. Like variola and vaccinia viruses, ectromelia viruses are cuboid. Their dimensions are 250 nm  350 nm and they have short crests on their surfaces. On the basis of these morphological criteria, orthopoxviruses can easily be distinguished from the smaller, ovoid parapoxviruses by rapid electron-microscopic diagnosis. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) African swine fever virus (▶ Sect. 19.7) is the sole member of the family Asfarviridae, represented in ultrathin cryosection. The four virus particles show different stages of maturity: the left virion is still in the process of being released from the cell by budding. The virus particles have a diameter of 200 nm and are isometric. Around the dense DNA-containing core, they exhibit a multilayer structure consisting of a protein capsid located between two lipid envelope membranes. Primary magnification  40,000, bar 100 nm. (Kindly provided by Germa´n Andre´s, Centro de Biologia Molecular Severo Ochoa, Madrid, Spain) Porcine parvovirus (▶ Sect. 20.1) as prototype of the family Parvoviridae, grown in cell culture, partially purified by gradient centrifugation and depicted after negative staining with uranyl acetate. The naked, isometric viruses are 25 nm in diameter and were occasionally penetrated by the contrast medium. Primary magnification  40,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Porcine circovirus 1 (▶ Sect. 20.2) representing the family Circoviridae, grown in cell culture, purified by gradient centrifugation and represented by negative staining using 1 % uranyl acetate. Porcine circoviruses are 17–18 nm in diameter, constituting the smallest autonomously replicating mammalian viruses. They are considerably smaller than avian circoviruses: chicken anaemia virus has a diameter of 22–25 nm and, in contrast to porcine circoviruses, has a clear capsid structure. Primary magnification  60,000, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany) Scrapie-associated fibrils (Chap. 21) purified and enriched roughly 10,000-fold from brains of scrapie-infected hamsters, represented by negative staining with 1 % uranyl acetate. The slightly “twisted” glycoprotein fibrils are proteinase K resistant and also characteristic of other transmissible spongiform encephalopathies in humans and animals. Primary magnification  31,500, bar 100 nm. (H.R. Gelderblom, Robert Koch Institute, Berlin, Germany)

Glossary

Aetiology The theory of the causes; in medicine and epidemiology, aetiology is the totality of factors that have led to a specific disease. Agglutination Clumping (adhesion) of antigen-carrying particles, such as red blood cells (hemagglutination), bacteria, viruses and viruses and infectious agents complexed with antibodies. Allergy (Greek aller´ıa, “foreign reaction”) The exuberant immune response to certain normally harmless environmental substances (allergens). An allergy manifests itself as a typical symptom caused by inflammatory processes. Anamnesis (Greek anάmnsiB, “memory”) The history of a patient with regard to his/her current afflictions. Anergy Lack of immune response by switching off the immune response against an antigen. Anergy is a permanent mechanism with which the immune system prevents T lymphocytes from attacking the body’s own tissues. T cells mature in the thymus during embryonic development. Autoreactive T lymphocytes, which recognize the body’s own antigens, and thus would attack the body’s own tissue, are generally eliminated. However, a few T cells reach the periphery of the embryonic organism. If these cells bind to an antigen through their T-cell receptor there, they become activated only in the presence of co-stimulatory molecules. If these co-stimulatory signals are lacking, the T cell remains permanently inactivated and inoperative. Antigen A substance that is recognized as foreign by the immune system, such as a protein, a carbohydrate structure or another chemical compound. Antigenicity Recognizability of a protein or other substance by the immune system. Even minor changes and variations in the amino acid sequence of a protein can alter antigenicity, thus changing serological detection by antibodies. Apical The term means “located at the top” and is used to indicate the side of a polarized cell which is located on the surface or in a lumen. The other side of a polarized cell is referred to as the basolateral side. Apoptosis Programmed cell death. Apparent/inapparent (Latin apparere, “become visible”). Becoming visible or invisible. The term is often used in connection with infections with or without symptoms. Arthralgia Joint pain.

S. Modrow et al., Molecular Virology, DOI 10.1007/978-3-642-20718-1, 961 # Springer-Verlag Berlin Heidelberg 2013 962 Glossary

Arthritis Acute or chronic, specific or nonspecific joint inflammation, articular rheumatism. Atrophy Tissue shrinkage. Arthropods Invertebrate, articulated animals having an exoskeleton, including insects, millipedes, crabs, spiders, scorpions and mites. Assembly See “Self-assembly” and “Viral assembly”. Attenuated viruses Virus mutants with a weakened virulence which arise sponta- neously or by continuous cultivation in cell culture. Infections with such viruses are usually either without or with significantly weakened symptoms. Attenuated virus strains are often used as vaccine viruses. Autocrine Direct effect of a molecule (cytokine, hormone, growth factor, etc.) released by a cell on the same cell, e.g. by binding to receptors on the cell surface. Basolateral The base of a polarized cell that is remote from the lumen in a cell layer and its lateral portions; see also “Apical.” Bilirubin Yellowish degradation product of haemoglobin which is coupled to glucuronic acid in the liver, and is excreted through the bile into the intestine. Bronchial lavage Lavation of the bronchial tree with isotonic solution for thera- peutic or diagnostic purposes. Bronchiolitis Inflammation of the bronchioles, i.e. the cartilage-free branches of segmental bronchi. Bronchitis Acute or chronic inflammation of the mucous membrane in the region of large and medium-sized bronchi, i.e. the continuation of the trachea for passage of air into the lungs. Bronchopneumonia A focal pneumonia without reference to anatomical lung limits. A common feature of inflammation foci, which can have various sizes and development stages, is exudate-filled alveoli in the infiltrated lung regions. Budding The process of releasing virus particles from cellular membranes by extrusion or evagination. Cap group (50-cap structure). 7-Methylguanosine modification of eukaryotic mes- senger RNA (mRNA) molecules attached at the 50 end, which is linked to the 50-OH group of the next nucleotide by a 50–50 bond. This and the adjacent nucleotide are modified by a methyl group at the 50-OH residue of the ribose. Capsid Icosahedral or helical virus particle structure which is composed of proteins. Capsomers Protein components that make up the capsids, composing one or more viral structural proteins. Carcinoma Malignant neoplasm of epithelial origin. Chaperone Catalysts of protein folding. Chaperones have the function of binding specifically to other proteins and of preventing non-specific aggregation or misfolding. Cholestasis Extrahepatic bile congestion in the large intrahepatic or extrahepatic bile ducts as a result of outflow obstruction, or with intrahepatic obstruction in the bile canaliculi as a result of a metabolic disorder of liver cells that alters their directional permeability (e.g. in viral hepatitis). It leads to an increase of the Glossary 963

levels of bile acid and certain liver-specific enzymes in the blood (e.g. glutamyl- transpeptidase and alkaline phosphatase). Chorioretinitis Inflammation of the choroid (choroiditis) with secondary inflam- mation of the retina (retinitis). Cirrhosis Progressive chronic disease which leads to induration by fibrosis and to a scarring contraction of an organ (usually the liver), resulting in death of functionally active tissue (parenchyma) by connective tissue proliferation due to chronic inflammation. Co-infection The concurrent infection of a human or animal with another pathogen (virus, bacterium, parasite, fungus). Confluence Coalescence or merging of exanthemas and skin efflorescence. Conjuntivitis Inflammation of the conjunctiva. Contagious Tending to spread, infectious. Contamination Infection/contagion of skin (hands), surfaces and objects by contact with materials that (possibly) contain infectious agents. Convulsions (Latin convolvere, “to curl,” “to roll together,” “to convolve”). Repeated, serial and involuntary muscular contractions. Croup A cough illness which particularly affects children aged between 6 months and 3 years because their larynx is very narrow owing to the still immature laryngeal development. During or as a result of infectious diseases, the mucous membrane of the larynx and the vocal chord region becomes inflamed and swells. In this way, the children develop respiratory difficulties and sticky mucus additionally constricts the airways. The term “croup” originally referred only to the cough that is associated with diphtheria. Cull Government-ordered killing of individual animals or the entire animal population of livestock without bleeding (see “Slaughter”) and with destruction of the undamaged carcasses. This measure prevents spread of pathogens through blood contact or aerosols. It is the usual process in the case of an outbreak of foot-and- mouth disease (picornavirus infection) or classical swine fever (flavivirus infection). Cytopenia (granulocytopenia, leucocytopenia, erythrocytopenia, lymphocytopenia, monocytopenia, neutrocytopenia, thrombocytopenia) Reduction of the number of the respective individual cells in the peripheral blood. Degermination (sterilization). See “Disinfestation.” Dermatitis Acute inflammation of the skin. It can be manifested by skin redness (erythema), swelling (oedema), lymph secretion (exudation) and the formation of blisters, crusts and scales (efflorescence). Diagnosis (Greek diάgnos, “examination” in the sense of distinction, decision, knowledge). Diagnosis is, in the ambit of health care (medicine, nursing, phys- iotherapy, psychology), the exact assignment of findings, diagnostic signs or symptoms to a specific illness or to a set of symptoms in the sense of a syndrome. The syndrome determined, together with the suspected cause and pathogenesis of the disease, results in the diagnosis. Diagnosis is the assignment of phenom- ena to a category and their interpretation. Disinfection A procedure in which the number of infectious agents is reduced to such an extent that an infection or its transmission can be excluded. 964 Glossary

Disinfestation (very rarely or hardly used in English in the German sense of Entwesung). Extermination of harmful rodents (particularly mice and rats). It plays an important role in control of epidemics, and is mandatory after culling of a herd to prevent dissemination of pathogens by rodents. Dyspnoea Breathlessness, respiratory distress, shortness of breath. Efflorescence Noticeable change in the skin as a result of disease (“skin blossom”). Embryopathy Damage to the embryo before birth, e.g. by infectious diseases of the mother. Encephalitis Acute or chronic inflammation of brain tissue. Encephalomyelitis Inflammatory alteration of the nerve tissue in the brain and spinal cord. Encephalopathy A non-inflammatory change of nerve tissue in the central nervous system. Characteristic of transmissible spongiform encephalopathies such as bovine spongiform encephalopathy. Endemic Constantly increased incidence of infections in a confined region or population. The prevalence of infection in this region/population (the incidence of all cases of a particular infectious disease in a population at the time of examination) remains largely the same, but is increased in relation to other regions/populations. The relevant geographical area is referred to as the endemic region. Enteritis Acute or chronic inflammation of the small intestine. Enterocytes By far the commonest cells of the epithelium of the small intestine, responsible for the absorption of different substances from food. Enterocytes have a characteristic apical brush-shaped membrane with microvilli. These increase the surface area tremendously, and are the basis for absorption. Envelope (viral envelope) External lipoprotein bilayer derived from cellular mem- branes (plasma membrane, nuclear membrane, membrane of the endoplasmic reticulum or the Golgi apparatus) in which the viral partially glycosylated envelope proteins are incorporated. The viral envelope surrounds the capsid or nucleocapsid as a membrane. Enzootic Endemic occurrence of an infectious disease in animals. Epidemic (Greek epidm´ıa, “stay,” “arrival”) The temporal and spatial accumula- tion of an infectious disease within a region and a human population. An epidemic occurs when the prevalence, i.e. the number of infections and the associated morbidity, increases in a given period. An endemic is the ongoing frequent occurrence of a disease in a confined area. Epidemic wave See “Panzootic.” Epitope Structure accessible to the immune system (antigenic determinant). Epitopes that are recognized by the variable domain of antibodies (immunoglobulins) are mostly located on the surface of particles and macromolecules such as proteins. They can be constituted by a region of a protein of four to six amino acids (sequential epitopes) or by structural, folding-dependent parameters (structural or discontinuous epitopes). Even protein modifications (such as sugars or phosphates) are recognized by antibodies as epitopes. However, epitopes recog- nized by T lymphocytes are peptide segments of proteins that form complexes with Glossary 965

MHC proteins and are derived from protein structures which are not exposed on the surface. These complexes are recognized by T-cell receptors. Erythema Skin redness with a more or less distinct boundary. It arises as a result of expansion and increased filling of blood vessels. It usually disappears under pressure. Exanthem Skin rash. Exudation Release of certain portions of the blood through altered vessel walls into adjacent tissue or into inner or outer surfaces of the body during inflammatory processes. Food and Agriculture Organization A special agency of the United Nations, with headquarters in Rome (Italy), founded in Canada in 1945. It comprises 192 member countries today. It has the task of improving worldwide the production and distribution of agricultural products in general and food in particular to ensure human nutrition and to improve living standards. It establishes, inter alia, the international standards for food safety. Fulminant (Latin fulminans, “like a flash,” “glossy”) Commonly used in connec- tion with infections associated with very severe symptoms. Ganglion (ganglion nervosum) Nerve cells and fibres surrounded by a capsule and with enclosing glial sheath cells, which are present as bulges along cranial nerves and spinal nerves or as cholinergic switches within the autonomic nervous system. Gastroenteritis Acute or chronic inflammation of the small intestine. Genotype The exact genetic configuration, i.e. the nucleotide sequence and the individual set of genes that are present in the genetic information (genome) of a virus. Distinguishable viral genotypes are characterized by a defined percent- age of different nucleotides, which is usually determined specifically for each virus type. Genus Taxonomic category ranking below family and above species, and which contains one or more species. Here, it is used to refer to virus classes (genera). Glomerulonephritis Inflammatory alterations in the kidneys which affect the renal glomeruli and tubules. This can lead to complete renal dysfunction. It is frequently found in immune complex diseases, since the deposition of complexes in glomeruli impairs the filtration processes. Haematogenous Dissemination of pathogens into organs through the blood. Haemorrhage/haemorrhagic Bleeding, associated with bleeding. Heat/rut Rutting period in sows (heat, hogging) or cows (rutting, bulling). During that period, animals exhibit striking behavioural changes, which indicate increased sexual receptiveness or willingness to mate. Rut occurs at the begin- ning of a sexual cycle, and is interrupted during pregnancy. A premature termi- nation of pregnancy leads to a re-entry into oestrus, which is specifically characterized by the German husbandry terms umrauschen (premature re-entry or return into heat for a sow) and umrindern (premature re-entry or return into the rutting period for a cow). Helminths (Greek elmins, “worm”) General term for multicellular, endoparasitic organisms (worms). 966 Glossary

Hepatitis Liver inflammation. Herd immunity The existing protection against infectious disease in a population. Hexon A protein surrounded by six neighbouring proteins in the faces of icosahe- dral virus particles. Humoral/humoral defence system Responses of the immune system related to body fluids (especially serum) and mediated by their contents. It refers to the non-cellular components of the immune system, i.e. particularly immunologi- cally active molecules in the blood serum, e.g. immunoglobulins (antibodies). Hydrops Pathological accumulation of fluid in body cavities or in the interstitial space. Hyperaemia Increased blood volume in part of the circulatory system or in the organ circulation; e.g. the additional circulation in an organ. Hyperplasia Abnormal enlargement of a tissue or organ caused by increased cell division, and the associated extraordinary increase in the number of cells. Hypertrophy Increase in the size of an organ or tissue by cell enlargement or by cell swelling (e.g. by increased water influx) when the original number of cells is maintained. Iatrogenic (Greek iatros, “physician”) Infections and diseases transmitted by physicians or through instruments used by them (surgical instruments, needles, etc.). Icosahedron A regular polyhedron (particle) with 20 equilateral triangles as faces and 12 vertices. Icterus (jaundice) A symptom that occurs in several different diseases (e.g. hepa- titis). It describes the yellowing of the skin, mucous membranes and the con- junctiva of the eye caused by an increased concentration of bilirubin. Immunoglobulins (antibodies) Proteins that are produced in vertebrates in response to specific antigens (pathogen structures). Immunosuppression (Latin supprimere, “suppress,” “repress,” “withhold”) A reduction or repression of the body’s own immune defence mechanisms. Immunosuppression can be caused by viral infections (e.g. by human immuno- deficiency virus) or by the use of medication (e.g. by administration of cortico- steroids, cyclosporine in organ or bone marrow transplantations and in the treatment of autoimmune diseases). Furthermore, there are also hereditary forms of immunodeficiency. Incidence The number of new disease cases in a time unit. Incubation period The time between infection (contact) with a pathogen and the onset of disease symptoms. Infarction Local tissue destruction (necrosis) caused by impaired circulation, commonly as a result of acute vessel occlusion (thrombus). Infection Attachment, penetration and proliferation of pathogens (viruses, bacteria, fungi, parasites) in an organism (human, animal, plant). If the organism develops disease symptoms during this process, then it is an infectious disease. Inflammation Specific or non-specific immune responses to various noxious agents (disease-causing agents, pathogens). Inflammations can be caused by chemical, mechanical, electrical, radiological or biological agents. The latter include infections with viruses, bacteria or parasites and their products. An inflammation Glossary 967

is characterized by sequentially structured phases: vascular reaction, increased vascular permeability, exudation, leucocyte migration (chemotaxis or phagocy- tosis) and proliferation of connective tissue. Classic signs of inflammation are redness, warmth, swelling, pain and restricted function. Infiltration Pathologically increased, frequently localized penetration or migration of normal, abnormal or foreign cells into certain regions of the body and/or organs. It is generally associated with immunologically active cells that migrate into the infected organs as a result of viral replication. Inoculation Introduction or transmission of pathogens or cellular material (inocu- lum) into an organism or a culture medium. Interstitium/interstice Space between the body organs or tissues. It is usually filled by (interstitial) connective tissue. Keratitis Inflammation of the cornea. Keratoconjunctivitis Inflammation of the cornea and the conjunctiva. Latent infection Form of infection where the virus remains in the body after primary infection without producing infectious viruses or causing disease symp- toms. The virus can be stimulated to replicate by certain internal or external stimuli, leading to recurrences of symptoms of primary infection. Latent infec- tions are caused, for instance, by herpesviruses. Leader Leader sequence at the beginning of proteins (leader peptide) or transcripts (leader RNA). Lesion Wound, injury or disruption of tissue structures in a living organism. Lethality Number of deaths in proportion to the number of new disease cases in a particular illness. Limitation (of an infection) Delimitation of an infection or viral replication at the entry site of the pathogen or at a specific organ, usually by the functions of the immune system. Lymphohaematogenic Dissemination of infectious agents into various organs via the blood and/or the lymph fluid. Mammillitis Inflammation of the nipple, or the teat in cattle. Maternal immune protection Immune system of newborns based on antibodies (immunoglobulins) that are transferred from the maternal circulatory system into that of the foetus during pregnancy, and which remain detectable up to the age of 4–6 months in humans. IgA antibodies are also transferred to nursing infants by colostrum and breast milk (enteral maternal immune protection). Meningitis Inflammation of the membranes (meninges) of the brain and/or spinal cord. Meningoencephalitis Inflammation of the brain and/or spinal cord membranes (meninges) concomitantly with inflammation of adjacent brain tissue. Metastasis/tumour metastasis A secondary focus of disease (secondary tumour) which is caused by spreading of single cells from a primary, usually persisting focus of disease or tumour cells into other body regions. MicroRNA See “RNA interference.” Morbidity Number of diseases (such as a result of an infectious disease) in relation to the total population in a given time span. 968 Glossary

Mortality Number of deaths (such as a result of an infectious disease) in relation to the total population in a given period. Mummification After death of a foetus during pregnancy, it may be “fossilized,” remaining primarily in this form in the uterus, and may be delivered on schedule. This is a typical symptom of parvovirus infection in pigs. Myocarditis Inflammation of the heart muscle (myocardium). Necrosis Local death of cells of a tissue in a living organism. Needlestick injury Bleeding and non-bleeding puncture, cut or scratch injury caused by medical personnel (physicians, nurses, laboratory personnel) with needles, scalpels or similar objects which were contaminated with patient blood or body fluids. Needlestick injuries are the commonest occupational injuries of health-care workers. These injuries can lead to transmission of infectious agents (e.g. human immunodeficiency virus, hepatitis B virus and hepatitis C virus). Neoplasm/neoplasia Formation of new tissue by abnormal growth of body tissues owing to unregulated, autonomous and unrestrained cell proliferation. Nosocomial (referring to hospital). Nosocomial infections are infections that can be acquired in health-care service units, hospitals or similar establishments. Notification In animal disease control, notification is mandatory for important, especially contagious diseases such as foot-and-mouth disease. In such a case, the suspicion of an outbreak must be reported to the veterinary authority. Even animal owners are subject to this requirement. This process should make possi- ble the immediate detection of an outbreak, and minimize the risk of dissemi- nation of the disease. Nucleocapsid Complex of capsid proteins and the viral genome (DNA or RNA). Obligation to notify According to legislature in most countries, certain infections are notifiable. In the case of viral infections, this means that detection of viruses, suspicion of infection, illness or death caused by diseases which are mentioned in the law should be reported to the respective authorities either personally or anonymously. The treating physician as well as hospitals and laboratories are obliged to report cases of such diseases. Oedema (Greek oı´dma, “swelling”) Discharge of fluid from the vascular system and accumulation in the interstitial space. Oedema manifests itself as swelling of the tissue with subcutaneous fluid accumulation or in specific organs (e.g. pulmonary oedema, cerebral oedema). Opportunistic pathogens/infection Viruses, bacteria, fungi and parasites which infect immunologically weakened organisms in order to spread very efficiently in them. The state of immunosuppression may be genetically determined, may be caused by infection with other pathogens (such as human immunodeficiency virus) or may be caused by therapeutic measures (e.g. after organ transplants). Outbreak-control vaccination (see “Ring vaccination”) A vaccination measure which is undertaken after outbreak of a disease in a population and can be regionally limited. Outbreak-control vaccination is required if the herd immu- nity in a population has fallen below a certain percentage. Outbreak-control vaccination is aimed at preventing further dissemination of the pathogen by Glossary 969

inducing a rapid protective immunity among people who could come into contact with it (neutralizing antibodies, etc.). Pandemic Country- and continent-wide spread of an infectious disease. A pandemic is not geographically confined to a particular region; this feature distinguishes a pandemic from an epidemic. Panzootic Pandemic spread of an infectious disease in animals. Paracrine The immediate effect of a molecule (cytokine, hormone, growth factor) released by a cell on neighbouring cells, e.g. by binding to receptors on their cell surface. Parenterally A general term for the way through which pathogens or substances (drugs, injections, infusions) penetrate into the human or animal body, circumventing the gastrointestinal tract, e.g. by intravenous (through a vein), intra-arterial (by an artery), intramuscular (through a muscle) or intraperitoneal (through the abdominal cavity) injection. Parotid glands The largest of the salivary glands located anterior and inferior to the ears. Parotitis Inflammation of the parotid glands. Pathogenicity The genetically determined ability of viruses (also bacteria or parasites) to induce a disease in humans or animals. Penton Viral protein associated with five neighbouring proteins at the vertices of icosahedral particles. Perinatal Refers to the period immediately before and after birth. Peritonitis Localized or diffuse inflammation of the peritoneum (membrane lining the abdominal cavity) which is usually associated with secretion and may lead to ascites (fluid accumulation in the abdominal cavity). It is a typical symptom of a feline infectious peritonitis. Persistent (Latin persistere, “to remain,” “to persevere”) Commonly associated with infections during which the pathogen cannot be eliminated by the immune system of the organism, remaining in the body for long periods and continuously multiplying, even though frequently only with a low replication rate. Petechiae Tiny, punctated skin or mucous membrane bleeding (capillary bleeding); single efflorescence of the purpura. Pharyngitis Inflammation of the pharynx. Pharynx The “throat” or “gullet” as a common section of the trachea and oesoph- agus. The pharynx is a muscle–mucosal tube which begins at the skull base and leads into the oesophagus. It is an open connection to the nasal and oral cavities and the larynx, and is accordingly divided into nasopharynx, oropharynx and laryngopharynx. Phylogenesis/phylogeny The evolutionary development and the genetic relation- ship of all living organisms at all levels of biological taxonomy. Within the frame of this book, it is mainly used for the relationships of viruses within a family and the evolution of viral traits. Planum nasolabiale The fusion of upper lip and nose in the muzzle of cattle. Planum rostrale The fusion of the upper lip and nose to the front plate in the muzzle of swine. 970 Glossary

Pleuritis/pleurisy Inflammation of the pleura. Pneumonia Diffuse or focal inflammation of the lungs. Interstitial pneumonia is a form of pneumonia in which the inflammatory exudate occurs especially in the pulmonary interstitium, i.e. the connective tissue in the lungs. Polykaryocyte See “Syncytium.” Polyserositis Inflammation of serous membranes, such as the peritoneum or the pleura. A typical symptom of feline infectious peritonitis, a coronavirus infection. Prenatal Before birth, related to the child. Prevalence Frequency of all cases of a particular disease in a population at the time of examination. Prodromal stage Preliminary phase to the actual disease, usually accompanied by non-specific symptoms such as malaise, headache and fever. Purpura Spontaneous, speckled petechial capillary bleeding in the skin, mucous membrane and subcutaneous tissue (subcutaneous tissue). In contrast to erythema, it does not disappear under pressure. Quarantine Statutory and limited period for which people or animals (including people and animals they come in contact with) with certain infectious diseases or suspected of being infected are isolated. The duration of the preventive quaran- tine depends on the incubation period of the suspected disease. Quasispecies A population of very similar but not identical viruses, especially RNA viruses. It arises by high mutation rates based on the low fidelity of RNA- dependent RNA polymerases of RNA viruses, which incorporate incorrectly pairing nucleotides with an error rate of about 104. Reading frame (1) Coding region of a gene that is translated into a protein. The start codon is in almost all cases an ATG triplet, which codes for methionine. An open reading frame is a coding sequence which does not contain a stop codon on the mRNA over a long distance after the start codon. Reading frame (2) One of the three possible alternatives to read the nucleotide sequence of a gene as a series of non-overlapping triplets (codons) which direct its translation into the corresponding amino acid sequence of a protein. Recurrence (Latin recurrere, “to come back,” “to run back,” “to return”) Relaps- ing (recurrent) symptoms of an infection. It is known particularly in herpesvirus infections, in which the pathogens remain latent in the organism. External stimuli can induce reactivation of the virus from latency, resulting in lytic viral replication, which is associated with clinical symptoms similar to those of the initial infection. Reinfection (secondary infection) A second infection with the same pathogen (virus, bacterium, etc.). Relapse Recurrence of a disease after complete healing or recovery. Relapses of infectious diseases can be caused by reinfection with the original pathogen (e.g. by herpesviruses that remain latently present in the organism after a primary infection) or by pathogens from a new disease focus. Rheumatoid factors Antibodies of different subclasses (IgM, IgG, IgA, IgE) which are directed as autoantibodies against specific epitopes of the body’s own IgG immunoglobulins. Glossary 971

Ring vaccination (German definition) A localized vaccination measure after out- break of an infectious disease in an animal population. Animals residing within a radius of 3–10 km (depending on the infection) of the infected zone are vaccinated. This measure prevents spread of the disease, and additionally allows the use of vaccinated animals. However, trade restrictions must usually be accepted. Ring vaccination (English definition) The vaccination of all susceptible individ- uals in a prescribed area around an outbreak of an infectious disease. Ring vaccination controls an outbreak by vaccinating and monitoring a ring of people around each infected individual. The idea is to form a buffer of immune individuals to prevent the spread of the disease (see “Outbreak-control vaccination”). RNA editing Post-transcriptional modification of the mRNA sequence by targeted insertion or excision of single nucleotides. RNA interference (RNA silencing) RNA interference is one of the mechanisms through which cells can regulate gene expression at the post-transcriptional level by controlling the sequence-specific degradation and thus the amount of mRNAs. RNA interference is based on the formation of microRNAs (miRNAs) or small interfering RNAs. These are single-stranded RNA molecules of 21–23 nucleotides in length which result from cleavage of longer pre-miRNA mole- cules. Pre-miRNAs are encoded in the genome of humans, mammals and plants in specific genes that are transcribed by RNA polymerase II and are post-transcriptionally modified with 50-cap groups and polyadenylated. They contain sequence regions that form intramolecular double-stranded hairpin structures, which are cleaved by the nuclear protein complex Drosha/Pasha, which possesses RNase III activity. The resulting pre-miRNAs are exported to the cytoplasm, where they are further processed into double-stranded miRNA molecules with a 30 overhang by Dicer, a cytoplasmic RNase III. A helicase unwinds miRNA duplexes to single-stranded miRNAs, each of which interacts with the RNA-induced silencing complex (RICS). The miRNA/RISC complex binds by the miRNA moiety to mRNAs that contain miRNA complementary sequences, directing the degradation of such transcripts. Besides pre-miRNAs, precursor miRNA sequences are also found within the introns of protein-coding sequences of mRNA molecules, which frequently induce the degradation of their own precursor molecules. Sarcoma Malignant, locally destructive, metastasizing tumour originating from mesenchymal tissues (soft tissue, skeletal and neurogenic tissue and the inter- stitial connective tissue of organs). Self-assembly Orderly autonomous assembly of various components (proteins and nucleic acid) into functionally intact units without requiring additional enzy- matic activities (e.g. the formation of ribosomal subunits, and infectious viruses; see also “Viral assembly”). Seroconversion The occurrence of antibodies in the serum of a patient who had been free of the corresponding immunoglobulins. Seroconversion occurs as a result of infection or vaccination. 972 Glossary

Seroprevalence The frequency of occurrence of antibodies which indicate a past or an existing infection in the blood in a group of people or a population. Serotype Serologically distinguishable variation within a virus subspecies owing to the ability to interact with specific antibodies. The serotypes of a viral species differ in their antigenic properties (surface structures that are recognized by the immune system). The classification into serotypes allows a subdivision of viral species, which is of particular interest from an epidemiological perspective. Because of the increasingly automated methods of nucleic acid sequencing, the different viral species are distinguished by determining their genotypes. Slaughter Killing of animals for human consumption, including stunning-bleeding slaughter. Killed animals are released for human consumption within the frame- work of the detection of specific animal diseases. An example is enzootic bovine leucosis, a retrovirus infection. Small interfering RNA See “RNA interference.” Squalene An organic, unsaturated compound of the group of triterpenes which is produced by all higher organisms. It is an adjuvant in vaccines, i.e. an additional immunological agent that increases the effect of vaccines. Stroma The interstitial connective tissue of an organ. Subarachnoid space The space containing cerebrospinal fluid between the arach- noid (i.e. the poorly vascularised, connective tissue, bilaterally covered with endothelial cells which sheathes the brain and spinal cord) and the pia mater (the connective tissue which lies directly on the brain and spinal cord surfaces and is tightly connected with the underlying membrane). Superinfection The concurrent or chronologically only slightly delayed secondary infection of an organism (human, animal, plant) with a different strain of the same pathogen or another pathogen (virus, bacterium, parasite, fungus). Because the first infectious agent causes damage to the host organism, other infectious agents can invade and spread very efficiently. Symptom Sign of disease. Symptomatic infection Infection associated with symptoms. Syncytium A multinucleated cell (polykaryocyte), also known as a giant cell. A syncytium can arise by fusion of several individual cells. This process is induced by some viruses (e.g. paramyxoviruses, herpesviruses) which promote the fusion of infected cells with uninfected cells by using the fusogenic activity of their surface proteins. Alternatively, syncytia can also arise by nuclear division without subsequent division of the cytoplasm. Syndrome (Greek sύndromoB, “coming together,” “path,” “run”). In medicine, syndrome means the simultaneous presence of various characteristics (symp- toms) which usually have a common cause. Synovial fluid The clear, viscous and ropy fluid produced by the synovium (joint- lining membrane) that reduces friction between the articular cartilages during movement. Tachypnoea Increased respiratory rate by stimulating the respiratory centre in the case of increased oxygen demand, e.g. during physical exertion, fever or reduced supply of oxygen (hypoxaemia) Glossary 973

Tegument Proteinaceous layer between the envelope and capsid in herpesviruses. Tonsils (Latin tonsilla, “almond”) Almond-shaped organs that are parts of the lymphoepithelial tissue of the lymphatic pharyngeal ring. Four different tonsils can be distinguished: pharyngeal tonsils (tonsilla pharyngealis or adenoidea), tonsils of the tongue (tonsilla lingualis), palatal tonsils (tonsilla palatina) and tubal tonsils (tonsilla tubaria). Tracheitis Inflammation of the trachea. Trailer Non-coding RNA sequence region at the 50 end of the genome of negative- sense RNA viruses (analogous to the 50 untranslated region). Transaminases (aminotransferases) Enzymes that catalyse the transfer of an a-amino group from a donor molecule, usually an amino acid, to an acceptor molecule, commonly an a-keto acid, e.g. pyruvate and oxaloacetate (transami- nation reaction), using pyridoxal phosphate as a coenzyme, including an exchange of the respective redox states. These enzymes include, inter alia, aspartate aminotransferase and alanine aminotransferase. The detection of elevated transaminase activity in serum is used as diagnostic evidence of liver inflammation or other damage to this organ. Tropism (Greek tropo´B, “change,” “turn”) Refers to the ability of a virus to infect a particular cell type (cell tropism), the cells of a specific tissue (tissue tropism) or an organ (organ tropism) and to multiply there. Host tropism means the preferred or exclusive infection of a given species as the host organism. Tumour (Latin tumor, “swelling,” “lump”) General term for any distinct swelling of body tissues (neoplasm). Ulcer (from Latin ulcus). Lesion of the skin or mucous membranes with disinte- gration and necrosis and loss of epithelial tissue, which usually heals by rejection of the necrotic tissue, leaving cicatrices. Ultrafilterable Designation for substances or particles which cannot be filtered by bacterial filtration systems, and thus are smaller than 0.2 mm. Undulating fever Wave-like disappearing and recurring fever. It is typical of infectious diseases in which a change of surface antigens occurs, leading to an immune response against the altered “new” pathogen. An example is equine infectious anaemia, a retrovirus infection. Vaccination (protective vaccination) A preventive measure against various infec- tious diseases by application of a vaccine. Vaccination stimulates the immune system to induce specific immunological defence mechanisms in order to estab- lish a specific immunity against the corresponding infectious disease. Vaccine A biological preparation composed of an attenuated (weakened) or inactivated (killed) pathogen that generates an immunity to a particular disease by stimulating antibody production or cellular immunity against the respective pathogen. Vascular Concerning blood vessels. Viraemia The occurrence and presence of virus particles in the blood. Virion Infectious virus particle. Virulence Sum of all the properties of a pathogen (virus) that contribute to disease development in a human or an animal. Virulence is quantified as the LD50 value, 974 Glossary

i.e. the number of viruses (or other pathogens) which are sufficient to kill 50 % of the animals or cells in a tissue culture. Viral assembly The orderly autonomous assembly of the viral structural proteins and viral genomes into infectious virus particles at the end of the viral replication cycle. World Health Organization A specialized agency of the United Nations that acts as a coordinating authority concerning international public health. It has its headquarters in Geneva (Switzerland). It was founded on 7 April 1948 and has 194 member states. World Organisation for Animal Health (OIE) The authority responsible for international animal health, with headquarters in Paris (France). It was founded in 1924 as the Office International des Epizooties on the occasion of a rinderpest outbreak (1920 in Belgium), and includes 178 member countries today. Zoonosis Infectious disease in which pathogens can be transmitted from animals to humans, causing a disease in them. Additional Information

In the various chapters, data concerning the notificability and epidemiology of individual virus infection refer mainly to the situation in countries of Central Europe. For readers with interest in respective data in other countries or regions worldwide, we attach a list of web sites that will supply actual data in English. For individual countries we would like to ask the readers to contact the web sites of global agencies or national health authorities and/or departments of health.

Human infectious diseases Global: WHO Infectious diseases: Global alert and response, databases and information system http://www.who.int/csr/resources/databases/en/index.html WHO – Europe: Centralised information system for infectious diseases CISID http://data.euo.who.int/cisid/ European Center for Disease Prevention and Cotrol (ECDC), Stockholm, Sweden Information on surveillance of infectious (communicable) diseases in Europe http://www.ecdc.europa.eu/en/activities/surveillance/disease_specific_surveillance/ Pages/disease_specific_surveillance.aspx

National: Australia: Department of Health and Aging, Australian Government, Information and surveillance of communicable diseases http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-communic-1 Austria: Bundesministerium fur€ Gesundheit, Notifiable infectious diseases and statistics http://www.bmg.gv.at/home/Schwerpunkte/Krankheiten/Uebertragbare_Krankheiten/ Canada: Public Health Agency of Canada: www.publichealth.gc.ca

S. Modrow et al., Molecular Virology, DOI 10.1007/978-3-642-20718-1, 975 # Springer-Verlag Berlin Heidelberg 2013 976 Additional Information

Infectious diseases, infection control guidelines and surveillance http://www.phac-aspc.gc.ca/id-mi/index-eng.php Germany: Robert-Koch-Institut, Berlin: List and numbers of notifiable infectious diseases in Germany http://www.rki.de/DE/Content/Infekt/SurvStat/survstat_node.html Great Britian: Health Protection Agency, London, Infectious diseases, infection control guidelines and surveillance http://www.hpa.org.uk/Topics/InfectiousDiseases/ Ireland: Health Protetion Surveillance Centre, Dublin, Information, surveillance and data of notifiable and communicable diseases http://www.hpsc.ie/hpsc/ NotifiableDiseases/ New Zealand: New Zealand Public Health Observatory, Auckland, Information on notifiable communicable diseases http://www.nzpho.org.nz/NotifiableDisease.aspx and surveillance: http://www.surv.esr.cri.nz/ Sweden: Smittskyddsinstitutet (smi), Solna, Infectious diseases, infection control guidelines and surveillance http://www.smittskyddsinstitutet.se/in-english/statistics/ Switzerland: Eidgeno¨ssisches Departement des Inneren, Bundesamt fur€ Gesund- heit, Surveillance and numbers of notifiable infectious diseases http://www.bag.admin.ch/k_m_meldesystem/index.html?lang¼de USA: Centers of disease control and infection, Atlanta, Informations about infec- tious diseases, notification and case numbers http://www.cdc.gov/ National Center for Emerging and Zoonotic Diseases: http://www.cdc.gov/ncezid/ National Center for Immunization and Respiratory Diseases: http://www.cdc.gov/ ncird/ National Center for HIV/AIDS, Viral hepatitis, STD and TB prevention: http://www.cdc.gov/nchhstp/

Animal infectious diseases Global: OIE (World Organisation for Animal Health): Collection and analysis the latest scientific information on animal disease control and OIE-listed diseases. http://www.oie.int/animal-health-in-the-world/oie-listed-diseases-2013/

National: Australia: Australian Animal Health Laboratory (CSIRO), East Geelong. http://www.csiro.au/en/Organisation-Structure/Divisions/Animal-Food-and-Health- Sciences.aspx Belgium: Veterinary and Agrochemical Research centre (VAR-CODA-CERVA,) Brussels. http://www.coda-cerva.be Additional Information 977

Canada: Canadian Food Inspection Agency (CFIA), Reportable and notifiable diseases: http://www.inspection.gc.ca/animals/eng/1299155513713/1299155693492 North American Plan for Animal and Pandemic Influenza: http://www.publicsafety.gc.ca/prg/em/pandemic/2012-napapi-eng.aspx Terrestrial Animal Disease Surveillance: http://www.inspection.gc.ca/animals/terrestrial-animals/diseases/surveillance/eng/ 1313720601375/1313720675875 Denmark: Technical University of Denmark, National Veterinary Institute (DTU Vet), Lindholm. http://www.vet.dtu.dk/ France: L’Agence nationale charge´edelase´curite´ sanitaire de l’alimentation, de l’environnement et du travail (ANSES), Paris. http://www.anses.fr/en Centre de coope´ration Internationale en Recherche Agronomique pour le De´velop- pement (CIRAD), Paris, Montpellier. http://www.cirad.fr Germany: Friedrich-Loeffler-Institut (FLI), Insel Riems. http://www.fli.bund.de/ Great Britain: Veterinary Laboratories Agency (VLA), now part of Animal Health and Veterinary Laboratories Agency (AHVLA): http://vla.defra.gov.uk/ Research and Surveillance Virology: http://vla.defra.gov.uk/science/sci_virology.htm Wildlife Diseases: http://vla.defra.gov.uk/science/sci_wildlife.htm Pirbright Institute (PI), Pirbright. http://www.pirbright.ac.uk/ Italy :Istituto Zooprofilattico Sperimentale della Lombardia e dell’ Emillia Roma- gna (IZSLER), Brescia. http://www.izsler.it/ Istituto Zooprofilattico Sperimentale delle Venezie (IZS-Ve), Legnaro. http://www.izsvenezie.it/ The Netherlands: Central Veterinary Institute (CVI), Lelystad, http://www.wageningenur.nl/nl/Expertises-Dienstverlening/Onderzoeksinstituten/ central-veterinary-institute.htm Poland: National Veterinary Research Institute (PIWet; NVRI), Pulawy. http://www.piwet.pulawy.pl/piwet7/index_a_eng.php Spain: Centro De Investigacio´n en Sanidad Animal (CISA), http://www.nadir-project.eu/nadir_project/call_for_access/open_facilities_avai- lable_for_access/centro_de_investigacion_en_sanidad_animal_cisa Instituto Nacional de Investigacio´n y Tecnologı´a Agraria y Alimentaria (INIA), Valdeolmos, Madrid. http://www.inia.es/IniaPortal/verPresentacion.action 978 Additional Information

Sweden: Statens Veterinarmedicinska Anstalt, Uppsala. http://www.sva.se/ Switzerland: Institute of Virology and Immunoprophylaxis/Federal Veterinary Office, Mittelh€ausern, Bern. http://www.bvet.admin.ch/index.html?lang¼en USA: Animal and Plant Health inspection service (APHIS), United States Depart- ment of Agriculture (USDA) and Centres for Epidemiology and Animal Health (CEAH), Information on notifiable communicable animal diseases. http://www.aphis.usda.gov/animal_health/index.shtml Index

A Adenoviridae, 23, 626, 708 AAV-2 replication, 889 Adenovirus, 36, 707–738 Abacavir, 609 association with specific diseases, 712 Abortive infection, 33 attachment, 727 adenovirus, 735 CAR binding, 728 Abortive polio, 214 cellular receptors, 712 ABO system, 244 characteristic prototypes, 709 ACE-2. See Angiotensin-converting enzyme 2 classification, 708 (ACE-2) diagnosis, 736, 738 Achong, B., 808 epidemiology and transmission, 738 Ackermann, W., 794 genome organization and structure, 711 Acquired immunodeficiency syndrome genome replication, 720 (AIDS), 40, 598, 605, 608 genome structure, 714 characteristic diseases, 603 immune response, 735 late phase, 602 keratoconjunctivitis, 735 Actin, 59 late proteins, 723 Actin filaments, 59 non-oncogenic, 734 Activated macrophages, 73 oncogenic adenoviruses, 734 Acute-phase proteins, 77 penetration, 729 Acute progressive infectious encephalitis, 405 protein VI, 729 Acute respiratory distress syndrome, 472 replication, 727 Acycloguanosine, 115, 117, 127. See Tab. 9.1 structure, 710 and Fig. 9.1 target organs, 712 Acyclovir, 117, 127, 765, 798, 801 therapy and prophylaxis, 736 Adefovir, 117, 124, 649 Adenovirus-associated RNA, 726–727 Adenain, 711, 723 Adenovirus-associated tumours, 734 Adenine translocator 3 (ANT3), 491 Adenovirus death protein, 721 Adeno-associated viruses (AAV), 876, Adenovirus particle structure, 710 886–887, 889–892, 897–898 Adjuvant, 142 gene therapy vectors, 891 Adult T-cell leukaemia, 611 latent infection, 891–892 Aedes, 269, 270, 474, 475 pathogenesis, 897–898 A. albopictus, 273, 306 proteins functions, 884 A. aegypti, 270, 273 replication, 889–891 A. africanus, 269 transmission, 897 A. haemagogus, 269 Adenosine analogue, 124 A. scutellaris, 273 Adenoviral E1A and E1B proteins, cell A. triseriatus, 474 transformation, 733 Aflatoxins, 646 Adenoviral fibre protein, 711 African Duvenhage virus, 354

S. Modrow et al., Molecular Virology, DOI 10.1007/978-3-642-20718-1, 979 # Springer-Verlag Berlin Heidelberg 2013 980 Index

African horse sickness virus, 545, 549–551 characteristic prototypes, 906 clinical features, 550 classification and characteristic prototypes, diagnosis and vaccines, 551 905 epidemiology and transmission, 549 genome, 906 pathogenesis, 550 human pathogenic, 910–912 African swine fever, 36, 286, 857, 860–862 protein functions, 909 control and prophylaxis, 862 structure, 906 epidemiology and transmission, 860 Anergic, 80 evasion of the host immune response, 861 Angiotensin-converting enzyme 2 (ACE-2), pathogenesis, 861 328 Aggresomes, 860 Animal and human pathogenic bunyaviruses, Agnoprotein, 657, 665 474–477 Aichi virus, 190 Animal diseases, controlling, 514 AIDS. See Acquired immunodeficiency Animal pathogenic adenoviruses, 736 syndrome (AIDS) Animal pathogenic arteriviruses, 315 AIDS-related complex, 602 Animal pathogenic asfarviruses, 860–862 Akabane virus, 474 Animal pathogenic astroviruses, 235–236 Alastrim virus, 846 Animal pathogenic birnaviruses, 526 Aleutian mink disease, 878, 902 Animal pathogenic caliciviruses, 245–247 clinical features, 902 Animal pathogenic circoviruses, 912–914 epidemiology and transmission, 902 Animal pathogenic coronaviruses, 335–336 pathogenesis, 903 Animal pathogenic flaviviruses, 285–288 Allander, T., 657, 895 Animal pathogenic herpesviruses, 817–818 Alloherpesviridae, 741 Animal pathogenic papillomaviruses, 704–705 Alphacoronavirus, 319 diseases, 705 Alphaentomopoxvirus, 832 Animal pathogenic paramyxoviruses, 411 Alphaherpes viruses, 54, 741, 791–792 Animal pathogenic parvoviruses, 898–904 Alphapapillomavirus, 679 evolution, 899 Alpharetrovirus, 613 Animal pathogenic picornaviruses, 224–225 Alphaviruses, 292 Animal pathogenic polyomaviruses, 673–676 glycoprotein E1, 299 Animal pathogenic poxviruses, 852–855 glycoprotein E2, 299 Animal pathogenic reoviruses, 545 6k protein, 299 Animal pathogenic rhabdoviruses, 368 non-structural proteins, 296–297 Animal pathogenic togaviruses, 306–309 structural proteins, 298 Annexin, 637 Aluminium hydroxide adjuvant, 142 Annulate lamellae, 788 Aluminium hydroxyphosphate sulphate Anopheles, 369 adjuvant, 142 ANT3. See Adenine translocator 3 (ANT3) Amantadine, 120, 124, 128, 487, 512 Antibodies, 86 Ambisense orientation, 35 infection-enhancing, 266 Amdovirus, 878 maternal, 90 A/M2 protein, 486, 513 somatic hypermutation, 89 influenza A viruses, 486 structure, 86 influenza viruses, 513 Antibody diversity, 89 Amyloids, 926 Antibody subclasses, 89 Analogue of the pocket factor. Antigen ELISA, 166 See Pleconaril Antigenic drift, 157, 503–505 Anamnesis, def, 152 influenza virus, 504, 505 Anaphylatoxins, 78 Antigenic shift, 157, 438, 503 Andes virus, 469 Antigen-presenting cells, 71, 73, 80, 81, 84–85 Andrews, C., 6, 478, 499 Antigens, definition, 70 Anelloviridae, 25, 875 Antioncogenes. See Tumour suppressors Anellovirus, 904–914 Antiretroviral therapy, 610 Index 981

Antisense RNA, 132 Asfarvirus, 36, 93, 857–862 Antiviral chemotherapeutic agents, 117, 120, animal pathogenic, 860–862 122–126 classification and characteristic prototypes, Antiviral drugs, 13, 115 858 molecular targets, 116–120 genome, 858 selection pressure, 130 particle structure, 859 Aphthovirus, 188, 190 replication, 860 cellular receptors, 206 structure, 858 Apodemus agrarius, 470 viral proteins, 859 Apodemus agrarius corea, 469 Asfivirus, 857 Apodemus flavicollis, 470 Asialoglycoprotein receptor, 637 Apoptin, 909 Asian flu, 158, 500, 504 Apoptosis, 49–51 Asophils, 110 Apoptosis-inducing mechanisms, 50 Aspergillus flavus, 646 Apoptotic vesicles, 50 Assemblin, 751 2A protease, 197 Astroviridae, 18, 229 Apurinic/apyrimidinic site, 767 Astroviruses, 229, 230 Aquabirnavirus, 522, 527 animal pathogenic, 235–236 Aquareoviruses, 534 classification and characteristic prototypes, Arenaviridae, 437, 438 229 Arenaviruses, 438–454 clinical features, 234 animal and human pathogenic, 448 epidemiology and transmission, 234 attachment, 446 genome, 230 characteristic prototypes, 440 genome organization, 231 classification and characteristic prototypes, human pathogenic, 234 439 immune response and diagnosis, 234 genome organization and structure, 440 particle structure, 230 natural host, 440 pathogenesis, 234 particle structure, 441 proteins, 232 penetration, 446 replication, 233 proteins functions and properties, 444 structure, 229 replication, 446 therapy and prophylaxis, 235 structure, 439 Astruc, J., 794 Armstrong, C., 448 Atadenovirus, 23 Arteriviridae, 19, 186, 318 Ataxia, 374, 929 Arterivirus(es), 309–317 Ateline herpesvirus, 758 animal pathogenic, 315 Attachment, 31, 483 arteriviruses, 310 of influenza viruses, 483 classification and characteristic prototypes, Attenuated viruses, 137–141 310 Attenuation, 137, 141 genome organization and replication, 312 Aujeszky, A., 821 genome organization and structure, 310 Aujeszky’s disease, 821 M protein, 314 Australian bat lyssaviruses, 353 non-structural proteins, 312 Autocrine stimulation, 61 N protein, 314 Autoimmune encephalitis, 403 protein functions and properties, 313 Autoimmune reactions, 90 replication, 314 Avery, O.T., 9 structural proteins, 314 Aviadenoviruses, 708 structure, 311 clinical features, 738 viral proteins, 312 pathogenesis, 738 Arthritis, 91 Avian adenoviruses, 738 Arthropods, as virus carriers, 149 Avian bornaviruses, 371, 373 Asfarviridae, 25, 286, 626, 857 Avian flu, 160, 507–508 982 Index

Avian flu (cont.) BiP; immunoglobulin heavy chain binding in Central Europa, 507 protein, 212 Avian Hepatitis E virus, 254 Birnaviridae, 21, 521 Avian infectious bronchitis virus, 319, 321, Birnaviruses, 35, 522 330, 335, 338–339 animal pathogenic, 526 clinical features, 338 characteristic prototypes, 522 diagnosis and prophylaxis, 339 classification and transmission, 522 epidemiology and transmission, 338 genome organization and gene expression, pathogenesis, 339 524 Avian influenza, 148, 411, 482, 500, 501, 510 genome organization and structure, 523 Avian leucosis virus, 613 particle structure, 523 control, 614 protein and functions properties, 522 epidemiology and transmission, 613 protein functions, 375 pathogenesis, 614 replication, 525 Avian leukaemia virus, 5 structural proteins, 525 Avian nephritis virus, 235 structure, 522 Avibirnavirus, 522 Bishop, J.M., 556 Avipoxvirus, 832 Bishop, R., 541 Azidothymidine, 117, 121, 122, Bittner, J.J., 556 126, 609 BK polyomavirus, 635, 669, 670 associated diseases, 669 and JC polyomaviruses diseases, 670 B Black smallpox, 848 Bacillus Calmette–Gue´rin, 96 Blood-brain barrier, 46 Bacterial artificial chromosomes, 793–794 Blood-cerebrospinal fluid barrier, 46 Bacteriophages, 5 Blood group antigens, 244 Bait vaccine, 368 Bluetongue disease, 547, 549 Bak proteins, 688 clinical features, 547 Balayan, M.S., 252 pathogenesis, 548 Baltimore, D., 11, 556 prophylaxis, 548 Bancroft, T.L., 273 recent spreading into Europa, 549 Bang, O., 5, 556 Bluetongue virus, 159, 547–549 Bank voles, 219, 470 epidemiology and transmission, 547 Barker, G., 282 of sheep, 545 Barre-Sinoussi, F., 556 B lymphocytes, 86–90 Barr, Y., 808 BNLF1, 781 Basophils, 71, 72 Bocavirus, 878, 883, 896 Bats, 420, 427 animal bocaviruses, 903–904 as carriers of rabies, 362 genome, 878 B-cell lymphoma, 780, 809 genome organization, 883 B-cell receptor, 782 human bocavirus, 895–897 Beak and feather disease virus, 905, 913 Boceprevir, 120 Beijerinck, M.W., 4 Body-cavity-based lymphoma, 782 Bel1, 560, 567 Bokay, J., 798 Bel2 protein, 584–585 Bonemeal, 941 Bel response element (BRE), 567 Booster vaccinations, 142 Betacoronavirus, 319 Border disease virus, 289 Betaentomopoxvirus, 832 Bordetella bronchiseptica, 411 Betaherpesvirinae, 805 Borna, 376 Betaherpesviruses, 745, 792–793 Borna disease virus, 47, 370, 376 Betapapillomavirus, 679 Bornaviridae, 20, 351, 370 Bet protein of spumaviruses, 584 Bornavirus, 370 Biosensors, 180 animal pathogenic, 376 Index 983

attachment and penetration, 375 live vaccines, 291 avian, 373 pathogenesis, 289 classification and characteristic recombination events, 290 prototypes, 371 Bowenoid papulosis, 698 envelope proteins, 374 2B protein, 204 epidemiology and transmission, 376 BPV-1, 687 genome, 371 BPV-4, 692 genome organization, 373 Bradley, D.W., 252 immune response and diagnosis, Brain infections, 46–47 378 Branched DNA Detection, 175 infections in humans, 377 Break-bone fever, 273 M protein, 374 Brevidensovirus, 877 particle structure, 372 Brivudine, 117, 801 pathogenesis, 377 Bruusgaard, E., 798 replication, 375 BSE. See Bovine spongiform encephalopathy ribonucleocapsid, 374 (BSE) structure, 371 Budding, 38, 498 viral proteins, 374 orthomyxoviruses, 498 Borrel, A., 5 Bunyamwera virus, 455 Bourgelat, C., 412 Bunyaviridae, 437, 455 Bovine coronavirus, 336 Bunyavirus, 41, 455–477 Bovine ephemeral fever virus, 369 animal and human pathogenic, 474 Bovine herpesvirus 1, 817–820 characteristic prototypes, 457 Bovine herpesvirus 2, 818–819 classification and characteristic prototypes, Bovine immunodeficiency virus, 456 559, 599 conserved genomic sequences, 460 Bovine leukaemia virus, 617 entry gates, 41 Bovine papillomavirus, 678 envelope proteins, 463 E5 protein, 785 Genome Organization and Structure, Bovine papillomavirus type 1 genome 460 structure, 684 Gn and Gc proteins, 459 Bovine parainfluenza virus.3, 411 human pathogenic, 469 Bovine parvovirus, 903–904 L segment, 460 Bovine respiratory syncytial virus, 416 natural hosts, 457–458 Bovine spongiform encephalopathy (BSE), particle structure, 459 30, 933, 939, 943 protein functions, 464 cases in various countries, 941 protein properties, 464 clinical features, 944 replication, 467 consumer protection, 943 S segment, 460 control, 945 structural proteins, 463 diagnosis, 945 structure, 456 emergence, 940 transmission by insects, 456 epidemiology and transmission, 940 viral proteins, 463 pathogenesis, 944 Burkitt, D., 808 scenarios for spreading, 940 Burkitt’s and Hodgkin’s lymphoma, spread scenarios, 940 741 Bovine viral diarrhoea virus (BVDV), Burkitt’s lymphoma, 808, 810, 812 257, 288–291 Bursa of Fabricius, 235, 527 clinical features, 288 BVDV. See Bovine viral diarrhoea virus control and prophylaxis, 291 (BVDV) epidemiology and transmission, 288 BZLF1, 755, 771 genome organization, 262 BZLF1 gene, 771 immune response and diagnosis, 289 BZLF1 protein, 771 984 Index

C Caprine arthritis encephalitis virus, 559, 618 C1, 78 Capripoxvirus, 830, 832, 853 C2, 78 Capsids, 27 C3, 78 selection pressure, 28 C3a, 78 Cap-snatching, 468, 488, 497 C3 convertase, 78 Cap-stealing, 446, 468 C4, 78 5’-Cap-stealing, 497 C5, 78 CAR. See Coxsackievirus and adenovirus C5a, 78 receptor (CAR) C6, 78 Carcinogenesis, 57–67 C7, 78 Carcinomas, 6 C8, 78 CARD. See Caspase activation and recruitment C9, 78 domains (CARD) Cachexin, 105 Cardiovirus, 188, 197 CAdV–1, 737 cellular receptors, 206 CAdV–2, 737 Carswell, 95 Caliciviridae, 18, 186, 236 Caspase activation and recruitment domains Calicivirus(es), 236–237 (CARD), 98 animal pathogenic, 245 Castleman’s disease, 815 characteristic prototypes, 237 Cat flu, 823 classification and characteristic prototypes, Cat flu feline calicivirus, 245 236 Cattle plague. See Rinderpest virus electron micrograph, 238 Caughey, B., 925 feline, 245 Caveolae, 537, 538 genome, 239 Caveolin-1, 537 human pathogenic, 242–247 Caveolin-3, 538 protein functions, 240 C3b, 78 structure, 237 c-bcl-2, 66 viral proteins, 238 CC chemokines, 108 California encephalitis viruses, 474 CCHFV. See Crimean–Congo haemorrhagic California virus serogroup, 455 fever virus (CCHFV) Calnexin, 82 CCL1, 109 Calomys laucha, 452 CCL2, 108 Calomys musculinus, 452 CCL3, 108 Canine adenoviruses, 737. See also CAdV CCL4, 108 epidemiology, 737 CCL5, 108 vaccines, 737 CCL6, 109 Canine distemper, 379, 382, 402, 413 CCL7, 109 clinical features, 414 CCL8, 109 diagnosis, 415 CCL9, 109 immuno-prophylaxis, 416 CCL11, 109 pathogenesis, 414 CCL13, 109 Canine distemper virus, 413 CCL16, 109 Canine herpesvirus 1, 823–824 CCL19, 109 Canine minute virus, 877, 903–904 CCL20, 109 Canine parainfluenza virus. 2, 411 CCL2/MCP-1, 109 Canine parvovirus, 877 CCL3/MIP-1a, 109 emergence, 157 CCL4/MIP-1b, 109 Canine parvovirus type 2, 899 CCL5/RANTES, 109 Cantegalovirus, 849 CCR5, 274, 575, 585, 586, 594, 607 Canyon, 32, 193, 201 CD3, 80, 82 Cap-binding complex, 212 CD4, 574, 584, 585 Cap-binding protein, 212 CD4+ cells, 602 Index 985

CD4 receptor, 31, 584, 585, 594 control and prophylaxis, 912 CD4+ T cells, 41 epidemiology and transmission, 912 CD8+ cytotoxic T lymphocytes, 80 genome organization, 908 CD8 receptors, 79 non-structural proteins, 908 CD14, 73 pathogenesis, 912 CD23, 61, 780 replication, 910 CD28, 584 Chickenpox, 798, 801 CD40, 80 Chikungunya virus, 159, 293, 306 CD46, 404, 728, 807 Chimpanzee coryza agent, 407 CD55, 207 Chordopoxvirinae, 830, 832, 833 CD56, 359 Choriomeningitis, 6 CD81, 265 Chow, L.T., 710 CD150, 809 Chronic wasting disease (CWD), 30, 921, 933, CD155, 205 936–938 CDK1, 63 Cidofovir, 118, 122, 127, 613, 673, 736, 805, CDK2, 63 814, 850 CDK4, 63 Circoviridae, 25, 875, 905 CDR, 585. See Complementarity determining Circovirus, 904–914 regions (CDR) characteristic prototypes, 905 CDw150, 394, 413 classification and characteristic prototypes, Cell-associated enveloped viruses. See CEV 905 particles genome, 906 Cell cycle, 62 genome organization, 908 Cell damage, 49–56 non-structural proteins, 907 Cell death. See Apoptosis; Necrosis particle structure, 907 Cell immortalization, 663 porcine, 913–914 Cell lysis, 223 protein functions, 909 Cell rounding, 51, 52 replication, 910 Cell transformation, 58 structure, 906 Cellular immune response detection, 177 cis-responsive element, 205, 209 Cellular interfering factor, 701 CJD. See Creutzfeldt–Jakob disease (CJD) Cervarix, 703 c-jun, 734 Cervical cancer, 696 Classical pathway, complement activation, 78 Cervical carcinoma, 698 Classical swine fever virus, 285–288 CEV particles, 831 clinical features, 286 Chang, Y., 815 control and prophylaxis, 287 Channel catfish, 741, 744 control in the European Union, 288 Chanock, R.M., 407 epidemiology and transmission, 286 Chargaff, E., 9 immune response and diagnosis, 287 Chase, M., 9 pathogenesis, 287 Cheetahs, 83 vaccine, 137 Chelle, P.-L., 919 Classic avian influenza, 478 Chemokine-receptor-like proteins, 774 Clathrin, 207 Chemokine receptors, 108, 584, 585 Claudin 1, 265 Chemokines, 45, 71, 95–113. See also CLEC5A, 275 Inflammatory chemokines Clethrionomys glareolus, 219, 470 constitutive (homeostatic), 110 Clinical features, 412 inflammatory, 110 Clonal selection, 90 Chemotherapeutic agents, antiviral, 13 Cloverleaf, 194 Chemotherapeutic index, 116 Cloverleaf structure, 205, 268 Chemotherapy, 115–132 3CLpro, 329 Chicken anaemia virus, 905, 912–913 c-myc, 646, 734, 812 apoptin, 909 Co-cultivation, 8 986 Index

Cohort killing, 945 Creutzfeldt, H.-G., 928 Colds, 44–45 Creutzfeldt–Jakob disease (CJD), 30, 919 Colony-stimulating factors, 110–111 clinical features, 929 Colorado tick fever virus, 22, 530, 545 epidemiology, 928 Colostrum, 90 variant, 929 Coltivirus, 529, 545 Crick, F.H., 9 Common vole, 470 Crimean–Congo haemorrhagic fever virus Complement activation pathways, 77 (CCHFV), 455, 469, 474–475 Complementarity determining regions infections, 474–475 (CDR), 86 CrmA, 840 Complement system, 77–79 Croup-associated virus, 379 Condylomata, 698 Crystallization or seeding model, 925, 926 Condylomata acuminata, 697, 698 Cuille, J., 919 Conjunctivitis, 46 Culex, 255, 293, 474, 475 Consensus sequences, 446 C. pipiens, 283, 877 Constitutive (homeostatic) chemokines, 110 C. univittatus, 283 Constitutive transport element (CTE), 592 Culicoides, 369, 474 Contact inhibition, 60 Culiseta melanura, 307 Copy choice recombination, 596 CWD. See Chronic wasting disease (CWD) Coronaviridae, 19, 186, 318, 335 CXC chemokines, 108 Coronavirus(es), 34, 318–339 CX3C chemokines, 108 accessory proteins, 328 CXCL2, 109 animal pathogenic, 335–336 CX3CL1, 110 bovine, 336 CXCL4, 109 classification and characteristic prototypes, CXCL6, 109 319 CXCL8, 109 feline, 335 CXCL9, 109 genome organization and replication, 322 CXCL10, 109 genome organization and structure, 319 CXCL12, 110 haemagglutinin esterase, 319 CXCR4, 574, 575, 584, 585, 594, 607 human pathogenic, 330–332 Cyclin-dependent kinase, 612, 664, 690 non-structural proteins, 323 Cyclin-dependent kinase 1, 666 particle structure, 321 Cyclins, 62 proteins overview, 324–326 Cyclophilin, 582, 595 replication, 328 Cyclophilin B, 692 structural proteins, 323 Cypovirus, 529–531 structure, 319 Cyprinid, 744 viral proteins, 323 Cytokines, 13, 43, 61, 82, 95–113 Cossart, Y, 892 Cytomegalovirus, 24, 43, 118, 741, 745, Cottontail rabbit papillomavirus, 699 756, 761 Cowpox virus, 852–853 clinical features, 803 clinical features, pathogenesis, 853 cytokine receptor-like proteins, 774 epidemiology and transmission, 852 E1 protein, 769 vaccination, 853 E2 protein, 770 Coxsackievirus(es), 6, 46, 187, 207, 217 evasion of the immune response, discovery, 187 92, 804–805 pathogenesis, 218 genome, 756 Coxsackievirus and adenovirus receptor immediate early genes, 770 (CAR), 32, 207, 727 immediate early proteins, 769 CP4, 767 immune evasion, 774 CPEB, 651 immune response and diagnosis, 804 3C protease, 197, 203 immunoglobulin-binding surface 2C protein, 204, 205 proteins, 761 Index 987

pathogenesis, 803 Dideoxyinosine, 118, 124, 571, 609 therapy, 805 Dideoxy-3’-thiacytidine, 118, 649 transmission, 801 Diehl, V., 808 Cytopathic effect, 7, 51, 52 Dilatative cardiomyophathy, 217 Cytopathogenic virus, 289 Dinovernavirus, 530 Cytoplasmic inclusion bodies, 53 Dipalmitoylphosphatidylcholin, 728 Cytorhabdovirus, 373 Distemper-associated enamel hypoplasia, 414 Cytosine analogue, 121 DIVA vaccines, 145 Cytosine arabinoside, 115 DnaJ chaperone, 663 Cytotoxic T cells, 80–83 DnaK, 663 DNA latency, 151, 894 DNA polymerase, viral, 36 D Dobrava–Belgrade virus, 455, 470 Dalldorf, G., 187 Doerr, R., 794 D and J segments, 89 Doherty, P.C., 6 Dandy fever, 273 Dot-blot, 168 Dane, D.S., 628 Double-stranded DNA viruses, 35–36 Dane particles, 628 Double-stranded RNA viruses, 35 DC-SIGN. See Dendritic-cell-specific DP, 85 ICAM-3-grabbing non-integrin DP1, 64, 65 (DC-SIGN) 3D polymerase, 203 Decay accelerating factor, 207 D protein of parainfluenza viruses, 392 Degen, K., 376 DQ, 85 Deinhard, F., 282 DQw3, 702 de la Torre, J.C., 370 DR, 85 Delavirdine, 119, 609 Duck hepatitis B virus, 637 Deltavirus, 649 as model system, 647 Demyelination, 47 Dulbecco, R., 8, 11 Dendritic cells, 42–44, 69, 70 Duncan’s syndrome, 809 Dendritic-cell-specific ICAM-3-grabbing a-Dystroglycan, 446 non-integrin (DC-SIGN), 334, 425, 585 Dengue fever, 269, 273 Dengue haemorrhagic fever, 273, 274 E Dengue shock syndrome, 269, 273, 274 E1A protein adenovirus, 715, 717 Dengue virus(es), 19, 255, 257, 273–276 Early proteins adenovirus, 715–723 attachment, 266 Eastern equine encephalitis virus, clinical features, 273 158, 294, 307 immune response and diagnosis, 275 EBER, 772, 811 pathogenesis, 274 EBER2, 776 serotypes, 274 EBNA1, 66, 777, 778, 780 therapy and prophylaxis, 275 EBNA2, 61, 65, 777, 778, 780, 782 type 1, 266 EBNA3, 778, 781 type 2, 266 EBNA-LP, 777 Densovirinae, 876–878 Ebolavirus, 14, 21, 151, 419, 426 Densovirus, 877 diagnosis, 430 Dependovirus, 25, 876 discovery, 426 Designer drugs, 115 envelope proteins, 424 Detection of viruses, new methods, 180 epidemiology, 426 d’Herelle, F., 5 genome, 420 Diabetes mellitus, 46, 218 genome organization, 423 Dicer, 98 NP protein, 423 Dideoxycytidine, 118, 121 protein functions, 422 Dideoxycytosine, 609 structure, 421 988 Index

Ebolavirus (cont.) Entry gates, 41–42 symptoms, 427 Envelope, 17, 28 therapy, 430 Envelope proteins, 443, 481–487 transmission, 427 of arenaviruses, 443 E1B protein influenza viruses, 481 adenovirus, 715, 717 retroviruses, 572 19 kDa adenovirus, 717 of rhabdoviruses, 358 55 kDa adenovirus, 717 env genes, 572 Echovirus(es), 187, 188, 206 Enzootic bovine leucosis, 557, 617 Ectromelia, 852 E4-ORF6 protein adenovirus, 717 Ectromelia virus, 852 Eosinophils, 71, 72 Eddy, B., 656 Ephemerovirus, 352 EEV particles, 835, 842, 843 Epidemic, definition, 148 E2F, 64, 65 Epidemic nephropathy, 455 Efavirenz, 119, 609 Epidemiology, 148 E4 genes, 721 Epidermal growth factor (EGF), 60 EGF, 691. See Epidermal growth factor (EGF) Epidermodysplasia verruciformis, Egg drop syndrome virus, 738 681, 696, 697 E3-gp19K, 718 Episome, 26, 36, 751, 789, 791 eIF-2, 101, 208, 212 Epitheliochorial placenta, 90 eIF-2a, 727 Epizootic diseases, 352 eIF-3, 212, 241 Epizootic haemorrhagic disease virus eIF-4, 202 of deer, 545 eIF-4A, 202 Epomops franqueti, 427 eIF-4F, 202 E protein, 323 eIF-4G, 211 E1 proteins c element, 595, 597 adenovirus, 715–717 Elion, G., 13, 115 of papillomaviruses, 683 ELISA, 167, 176 E2 proteins ELISA to detect specific antibodies, 167 adenovirus, 716 Ellermann, V., 5, 556 of papillomaviruses, 686 E3L protein, 841 E3 proteins adenovirus, 718, 721 Embryopathies, 46 E4 proteins adenovirus, 721–723 Emerging virus diseases, 151 E proteins of coronaviruses, 327 Encephalitis, measles-associated, 405 E6 proteins of papillomaviruses, 687 Encephalitis viruses, 276 E7 proteins, papillomavirus, 65 Encephalomyocarditis virus, IRES, 196 Epstein, A., 808 Endemic diseases, definition, 148 Epstein–Barr virus, 8, 24, 55, 58, 61, 91, 112, Enders, J.F., 187, 407 741, 757, 760, 777–782, 784, 808–815 Endosomes, 29 attachment and penetration, 788 Endotheliochorial placenta, 90 BZLF1 protein, 773 Enfuvirtide, 120, 128, 609 clinical features, 809 Enhancers, def, 9 EBER RNA, 772 Entencavir, 649 epidemiology and transmission, 808 Enterovirus(es), 120, 188, 189, 191 genome, 757 cellular receptors, 206 genome structure, 753 clinical features, 217 immediate early genes, 772 epidemiology and transmission, 216 immune evasion, 92 immune response and diagnosis, 219 immune response and diagnosis, 813 pathogenesis, 218 induction of proliferation, 65 therapy and prophylaxis, 219 inhibition of apoptosis, 66 Entomobirnavirus, 21, 523 latency genes, 772 Entomopoxvirinae, 830, 832 latency proteins, 777, 778 Index 989

latent infection, 793 Exotic ungulate encephalopathy, 921 latent infection cycle, 793 Exportin, 491 LMP proteins, 782 Extracellular enveloped viruses. See EEV pathogenesis, 810 particles primary infection, 810 Extracellular matrix, 59 protein nomenclature, 755 Eyach virus, 530, 545 subtypes, 780 therapy, 814 transcription of immediate early genes, 779 F Epstein–Barr virus infection Falke, D., 740 chronic active, 811 Famciclovir, 119 secondary diseases, 812 Fas-associated death-domain-containing time course of antibody formation, 814 protein, 99 Epstein–Barr virus nuclear antigen Fatal familial insomnia (FFI), 919, 930 (EBNA)1, 61, 66 clinical features, 930 Equine arteritis virus, 310, 315–316 symptoms, 930 clinical features, 316 Fc receptor, 86 epidemiology and transmission, 315 Fc region, 87 immune response and diagnosis, 316 Feinstone, S.M., 219 pathogenesis, 316 Feline astrovirus, 235 Equine encephalitis virus(es), 306–309 Feline calicivirus, 241, 245 clinical features, 307 clinical features, 245, 246 control and prophylaxis, 308 epidemiology and transmission, 245 enzootic and epizootic cycles, 308–309 genome organization, 239 epidemiology and transmission, 306–309 Feline coronavirus, 318, 335, 337–338 immune response and diagnosis, 308 diagnosis, 338 Equine encephalosis virus, 530, 550 epidemiology and transmission, 337 Equine herpesviruses, 821–823 pathogenesis, 337 clinical features, 822 prophylaxis, 338 epidemiology and transmission, 821 Feline herpesvirus, 823 pathogenesis, 822 Feline immunodeficiency virus (FIV), 557, 621 Equine infectious anaemia virus (EIAV), 557, clinical features, 622 559, 620 control, 622 clinical features, 620 diagnosis, 622 diagnosis and control, 621 epidemiology and transmission, 621 epidemiology and transmission, 620 genome structure, 564 genome structure, 564 pathogenesis, 622 pathogenesis, 621 Feline infectious peritonitis virus, 318, 337. Equine influenza, 315, 501 See also Feline coronavirus Equine sarcoid, 704, 705 Feline leukaemia virus (FeLV), 57, 557, 615 Erbovirus, 190 clinical features, 615 E4 region, 721 epidemiology and transmission, 615 Erythema infectiosum, 892 genome structure, 564 time course of the disease, 895 infection diagnosis, 616 Erythrovirus, 876 pathogenesis, 616 genome organization, 883 subtypes, 615 European brown hare syndrome virus, 246 vaccine, 616 Evans postulates, 10, 153 Feline panleucopenia virus, 157, 877, 898–900 Exanthema subitum, 806 Feline parvoviruses Exanthems, 45 amino acid residues determining the host Excess mortality, 148 range, 900–901 Exonucleolytic proofreading, 156, 280, 571, clinical features, 899 597, 668 Feline sarcoma virus, 615 990 Index

Feline spongiform encephalopathy, FMD virus. See Foot-and-mouth disease 921, 945 (FMD) virus Feng, Y., 586 Follicular dendritic cells, 71 Fetopathies, 46 Fomivirsen, 132 FFI. See Fatal familial insomnia (FFI) Food poisoning, 243 Fibrinogen, 77 Foot-and-mouth disease (FMD) virus, 1, 194, Fibroblast growth factors, 60 205, 206, 224, 226 Fibroblast interferon, 97 clinical features, 227 Fifth disease, 892 control and prophylaxis, 228 time course of the disease, 895 epidemiology and transmission, 226 Fijivirus, 530 in Europa, 225 Filoviridae, 21, 351, 419 in Europe, 225 Filoviruses, 419, 426 immune response and diagnosis, 228 attachment, 425 L protein, 197 characteristic representatives, 419 pathogenesis, 227 envelope proteins, 424 proteins, 198 genome, 420 serotypes, 228 genome organization, 423 vaccination, 228 GP proteins, 425 Fortovase, 119 human and animal pathogenic, 426 Fosamprenavir, 130 nucleocapsid proteins, 423 Foscarnet, 119, 128, 805 proteins, 422 Fowl plague virus, 501 replication, 425 F-protein-mediated membrane fusion, 391 safety precautions, 420 F proteins, 382, 383 structure, 420 of morbilliviruses, 386 Findlay, G.M., 12, 95 paramyxoviruses, 381 Finlay, C., 270 Fractalkine, 108, 774 Flat condylomata, 697 Fraenkel-Conrat, H., 9 Flaviviridae, 19, 186, 255, 256 Francis, T., 478 Flavivirus(es), 41, 254–291 Franklin, R., 9 animal pathogenic, 285–288 Frosch, P., 4, 187 attachment, 265 Fro¨sner, G., 219 characteristic prototypes, 255 Fusion protein, 33 classification and characteristic prototypes, 255 entry gates, 41 G genome, 257 Gag, 579 genome organization, 262 Gag–Pol fusion protein, retroviral, 570 human pathogenic, 269 Gag–Pol precursor proteins, 594 non-structural proteins, 263 retroviral, 570 NS4A protein, 264 Gag precursor proteins, 567 NS1 protein, 263 Gag proteins, 567 NS2 protein, 264 Gajdusek, D.C., 920, 925, 939 NS3 protein, 264 Gallid herpesvirus 1, 825 NS5 protein, 264 Gallid herpesvirus 2, 824–825 particle structure, 257 Gallo, R., 58, 556, 598, 611 polyprotein, 258 Gammaentomopoxvirus, 833 proteins, 259–260 Gammaherpesvirus, 745, 793–794 replication, 265 Ganciclovir, 119, 122, 127, 765, 805, 814 structural proteins, 261 Gardasil, 703 structure, 256 Gastric lymphoepithelial carcinomas, 810 Flexal virus, 439 GB virus, 282 Flying foxes, 160 GB virus C, 256 Index 991

G-CSF, 111 HAdV-2, 711, 731 Geminiviruses, 905 main products of the E1 region, 716 General rinderpest eradication programme, 413 open reading frames, 714 Gene therapy, retroviral vectors, 597 HAdV-3, 732 Gene therapy vectors, 891–892 HAdV-4, 732, 736 Genetic reassortment, 157 vaccine, 736 Genuine flu, clinical features, 508 HAdV-5, 715, 731, 734 Gerstmann–Str€aussler–Scheinker (GSS) main products of the E4 region, 722 syndrome, 919, 930 HAdV-7, 731, 736 clinical features, 930 vaccine, 736 Giant cells, 53 HAdV-12, 708, 731, 734 Glomerulonephritis, 450, 902 HAdV-31, 731 Glycophorin A, 888 Haemagglutination, 168 GM-CSF, 111 activity, 380 Goatpox virus, 853–854 test, 168 Goats, 618 Haemagglutination-inhibition test, 168, 176 Goodpasture, E.W., 8 Haemagglutinin, 31, 478, 481, 484, 488–489 gp41, 560, 561, 572–574, 586, 594 of influenza A viruses, 484 gp120, 31, 129, 560, 561, 572–574, 585, 586, structure, 488 593, 594 Haemagglutinin esterase, coronavirus CD4 binding, 574 (HE), 319 CD4 receptor interaction, 575 Haemagglutinin esterase fusion (HEF), 327 GPC precursor protein of arenaviruses, 443 Haemagglutinin-esterase fusion (HEF) GPC protein, 442 protein, 478 G protein Haemagglutinin-neuraminidase, 380 paramyxoviruses, 382 Haemochorial placenta, 90 rabies virus, 366 Haemophilus influenzae, 400, 493 rhabdovirus, 354, 358 Haemorrhagic fever, 452–454 Graham, H., 273 clinical features, 453 Granulocyte-macrophage colony- epidemiology and transmission, 452 stimulating, 73 immune response and diagnosis, 454 Granulocytes, 69, 71 vaccine, 454 Granzymes, 82 Haemorrhagic fever with renal syndrome Gregg, N., 6, 301 (HFRS), 469 Gregg syndrome, 302 Haemorrhagic septicaemia of trout, 369 Gross, L., 6, 656 Hahn, B., 598 GRP-78. See BiP; immunoglobulin heavy Hairy cell leukaemia, 613 chain binding protein Hammerhead, 29 Gruter,€ W., 6, 794 Hamster disease, 448 GSS. See Gerstmann–Str€aussler–Scheinker Hantaan virus, 463, 468, 469 (GSS) syndrome Hantavirus, 21, 455, 456, 458–460, 463–467, Guanarito virus, 439, 452 469–474 Guanosine analogue, 127 clinical features, 471 Guarnieri, G., 7 discovery, 471 Gumboro virus, 21, 522, 523, 526 epidemiology and transmission, 469 Gut-associated lymphatic tissue, 42 G protein, 460 Gyrovirus, 905 L protein, 466 N protein, 465, 466 nucleocapsid components, 465 H particle structure, 459 HAART. See Highly active antiretroviral pathogenesis, 472 therapy (HAART) replication, 467 Hadlow, W., 920 structure, 459 992 Index

Hantavirus (cont.) epidemiology and transmission, 219 symptoms, 471 immune response and diagnosis, 221 transcription, translation and genome mini epidemics, 222 replication, 463 in mussels, 220 viral proteins, 460 pathogenesis, 221 Hantavirus cardiopulmonary syndrome therapy and prophylaxis, 222 (HCPS), 469, 470 Hepatitis B virus, 11, 23, 55, 58, 627, 628 HA protein, 484, 486, 500. See also acute virus infection, 642 Haemagglutinin attachment and penetration, 637 crystallographic structure, 484 chronic infection, 645–646 functionally domains, 484 clinical features, 642 influenza viruses, 486 epidemiology and transmission, 641–642 interaction with N-acetylneuraminic evading the immune response, 66 acid, 484 genome, 629, 632 subtypes, 500 genome integration, 645 Hard pad disease, 88 genome organization, 631 Hausen, H. zur., 12, 678 genotypes, 642 HBcAg, 628, 630, 633, 634 HBeAg-negative, 645 precore, 638 HBx Protein, 636 HBeAg, 633, 634 immune response and diagnosis, 648 HBsAg, 143, 628, 629, 634–636 infectious and non-infectious particles, 630 HBx protein, 646 mutations, 641 HCPS. See Hantavirus cardiopulmonary pathogenesis, 642 syndrome (HCPS) perinatal infection, 644 HDAg variants, 650 P protein, 636 HEF. See Haemagglutinin esterase primary liver cell carcinoma, 645 fusion (HEF) proteins, 635 HEF protein. See Haemagglutinin-esterase reading frame, 633 fusion (HEF) protein replication, 637, 638 Heine, J. von, 187 serological parameters of infection, 648 Hendra virus, 160, 380, 381, 417 subtypes, 641 clinical features, 418 therapy and prophylaxis, 649 Hendrickson, W., 574 vaccination programmes, 643 Henipavirus, 381, 393, 417 vaccine, 649 epidemiology and transmission, 417 Hepatitis C virus, 11, 58, 255, 256, Henle, G., 808 278–282 Henle, J., 10 attachment, 265 Henle–Koch postulates, 10 clinical features, 279 Henle, W., 808 discovery, 279 Hepacivirus, 256 epidemiology and transmission, 278 Hepadnaviridae, 23, 626, 627 genotypes, 278 Hepadnaviruses, 627–654 immune response and diagnosis, 281 classification and characteristic 7 kD protein, 264 prototypes, 627 non-structural proteins, 264 genome, 629 NS4A protein, 264 human pathogenic, 641–654 pathogenesis, 279 structure, 628 polyprotein, 258 Hepatitis, 46, 627, 642 proteins, 258 acute, 643 quasispecies, 280 chronic aggressive, 642 replication, 265 chronic persistent, 642 therapy and prophylaxis, 282 Hepatitis A virus, 188, 190, 194, 212, 219, 220 Hepatitis delta antigen, 650 clinical features, 220 Hepatitis D virus, 649–654 Index 993

epidemiology, clinical features and tegument, 751 pathogenesis, 653 tegument proteins, 761 genome and replication, 651 therapy, 798 genomic structure and replication, 652 thymidine kinase mutants, 765 immune response and diagnosis, 654 uracil glycosilase, 764 structure and viral proteins, 650 Herpes simplex virus 1, 784 therapy and prophylaxis, 654 Herpes simplex virus 2, 784 Hepatitis E virus, 19, 248, 252–253 Herpes simplex virus types Avian, 254 epidemiology and transmission, 794 classification and characteristic prototypes, type 1, 795 248 type 1varicella-zoster virus, 117 clinical features, 253 Herpesviridae, 24, 626, 741 epidemiology and transmission, 252 Herpesvirus, 32, 36, 43, 740–825 genome, 249 animal pathogenic, 817 genomic organization, 250 attachment, 787 particle structure, 250 characteristic prototypes, 742–744 pathogenesis, 253 classification and characteristic prototypes, replication, 251 741 structure, 249 entry mediator, 788 viral proteins, 249 envelope proteins, 758 Hepatitis G virus, 155, 256, 282 evasion of the immune response, 804 Hepatitis-splenomegaly syndrome, 254 genome, 751 Hepatocellular carcinoma, 643, 645 genome replication, 766 Hepatovirus, 188, 190 glycoproteins, 758 cellular receptors, 206 immediate early proteins, 767 Hepeviridae, 19, 186, 257 immune evasion, 92 Hepevirus(es), 248–254 induction of cell cycle arrest, 790–791 characteristic prototypes, 248 inhibition of DNA polymerase by protein functions and properties, 251 acycloguanosine, 127 HE protein esterase activity, 327 latency, 741 Herd immunity definition, 148 latent infection cycle, 791 Herpes, 794 latent stage, 775 Herpes genitalis, 795 lytic cycle, 789 Herpes immunological paradox, 8 lytic infection cycle, 788 Herpes labialis, 795 mutations, 131 Herpes neonatorum, 795 nomenclature of herpesvirus proteins, Herpes simplex virus, 6, 8, 24, 40, 43, 51, 53, 754–755 54, 92, 741, 794–798 non-structural proteins, 763 associated encephalitis, 796 proteins, 747 clinical features, 795 proteins involved in attachment and diagnosis, 797 interaction with cellular surface DNA polymerase, 765 components, 784 genome structure, 753 proteins involved in replication, 763, 764 helicase-primase complex, 765 proteins of the lytic cycle, 758 immediate early proteins, 767 proteins with homologies to cellular gene keratitis, 113 products, 774 latency, 54 replication, 787 LAT RNA, 776 replication proteins, 764 oriLyt-binding protein, 765 residence, 151 particle structure, 746 ribonucleotide reductase, 767 pathogenesis, 796 structural proteins, 747–750 processivity factor, 765 structure, 745 structural proteins, 758 thymidine kinase, 765 994 Index

Herpesvirus (cont.) pathogenesis, 604 updated taxonomy, 741 primary infection, 600 uracil DNA glycosylase, 766 quasispecies, 597 Herpesvirus 6 receptors, 585 clinical features, 806 serological window, 608 immune response and diagnosis, 807 subtypes (clades), 566 Herpesvirus 7, epidemiology and transmission, therapy and prophylaxis, 609 806 third infection phase, 602 Herpesvirus 8 variants, 600, 610 genome, 758 variants (quasispecies), 573 K-bZIP, 772 HIV-1, 159, 598 latency, 772 attachment, 574 latent infection cycle, 793 emergence of new variants, 600 Herpesvirus ateles, 757 Gag and Gag–Pol proteins, 568 Herpesviruses 1 and 2, 752–754 genome structure, 564 Herpesvirus saimiri, 757 glycoproteins, 573 Herpetic keratitis, 794 LTR region, 566 Hershey, A.D., 9 Nef protein, 583 Heterodimer model, 925 neutralizing antibodies, 574 Hexon-associated proteins, 711 particle structure, 561 Hexons, 710 properties of proteins, 569 HFRS. See Haemorrhagic fever with renal rev protein, 579 syndrome (HFRS) structure, 560 Highly active antiretroviral therapy (HAART), subtypes, 159 121, 131, 609, 670 Tat protein, 575, 577 Hilleman, M., 656, 675 vpu protein, 582 Hipposideros larvatus, 418 HIV-2, 159, 556, 599 Histamine, 72 Nef protein, 583 Hitchhiking (passenger) mutations, 156 subgroups, 599 HIV, 8, 14, 22, 40, 556 Vpx protein, 582 acute, 603 HIV proviruses, 610 antibodies against HIV, 608 HIV variants, 600, 601 attachment, 585 HLA-A2, 612 CCR5 receptor binding, 284 antigen-binding groove, 83 of CD4+ lymphocytes, 593 HLA-B35, 607 CD4 receptor, 573 HLA-B53, 607 cellular interaction partners, 574 HLA-B4002, 612 chemotherapy, 117, 119, 120 HLA-B4006, 612 clinical categories, 603 HLA-B4801, 612 clinical progression, 606 HLA-B5401, 612 clinical stages of HIV infection, 601 HLA-Cw8, 612 diagnosis, 608 HLA haplotypes, 83 early infection phase, 604 HLA type failure of vaccine development, cofactors involved in carcinogenesis, 702 610 risk of developing carcinomes, 702 high mutation rates, 605 H1N1, 151, 160, 499–501, 505, 507 immune evasion, 92 H2N2, 499, 500 importance of cytotoxic H3N2, 499, 500, 506 T cells, 607 H3N8, 501 infection course, 600 H5N1, 160, 500, 501, 506 integrase, 572 H5N2, 501 latency phase, 600 H7N1, 501 NSI strains, 601 H7N7, 501 Index 995

HN protein Human adenovirus, 708. See also HAdV of paramyxoviruses, 381 classification epidemiology and of respiro-and rubulaviruses, 386 transmission, 731 Hodgkin’s lymphoma, 808, 810 clinical features, 732 Hogle, J., 201 oncogenic potential, 733 Homologous transmission, 149 pathogenesis, 732 Hong Kong flu, 158, 500, 504 serotypes, 731 Hoogen, B. van den, 409 Human and animal pathogenic arenaviruses, Hoppegarten cough, 501 448–454 Horizontal transmission, 149, 556 Human and animal pathogenic filoviruses, 426 Horsepox, 850 Human and animal pathogenic Hoskins, M., 12, 95 orthomyxoviruses, 498–514 House mouse, 438, 448 Human and animal pathogenic HPV, 678 paramyxoviruses, 417 associated cancer, 697–702 Human B-lymphotropic virus, 806 associated skin warts, 699–700 Human bocavirus, 876, 895 classification, 681 clinical features, 896 cofactors involved in carcinogenesis, genotypes, 896 699 pathogenesis, 896 skin lesions and tumour diseases, 697 proteins functions, 884 vaccine, 703 Human coronaviruses, 328, 330 HPV-5, 696 clinical features, 331 HPV-6, 689 epidemiology and transmission, 330 protein nomenclature, 755 NL63, 328 HPV-8, 687 pathogenesis, 331 protein nomenclature, 755 Human cytomegalovirus, 753, 784, 801–805 HPV-11, 689, 692 clinical features, 802 HPV-16, 687, 887 epidemiology and transmission, 802 cervical cancer, 696 genome structure, 753 E6 protein, 687 immune response and diagnosis, 804 E7 protein, 689 Human enterovirus B, 194 genome structure, 684 Human enteroviruses, 18, 216–219 HPV-18, 687 Human hepatitis B virus, 627, 641–649 cervical cancer, 696 Human herpesvirus 3, varicella-zoster virus, E7 protein, 689 756–757 HPV-33, 692 Human herpesvirus 4. See Epstein–Barr virus Hsc70, 663 Human herpesvirus 5. See Cytomegalovirus Hsp70 chaperones, 663 Human herpesvirus 6, 743, 757, 784 hTERT, 688 clinical features, 806 HTLV, 61, 556 epidemiology and transmission, 806 diagnosis, 613 genome structure, 753 epidemiology and transmission, 611 latent infection, 792 pathogenesis, 612 pathogenesis, 807 primary infection, 611 therapy, 807 replication cycle, 595 Human herpesvirus 7, 757, 784 therapy, 613 genome, 757 HTLV-1, 611 pathogenesis, 807 genome structure, 564 therapy, 807 LTR region, 566 Human herpesvirus 8, 741, 758, 782–787, pathogenesis, 612 815–817 HTLV-2, 611 clinical features, 815 TAX proteins, 578 diagnosis, 816 HTLV-1-associated myelopathy (HAM), 611 epidemiology and transmission, 815 996 Index

Human herpesvirus 8 (cont.) HVP-16, E5 protein, 691 genome structure, 753 Hyalomma immune evasion, 92 Hyalomma, ticks, 474 latency proteins, 783 Hybrid capture assay, 175 latent phase, 793 Hydrophobia, 362 pathogenesis, 816 Hydrops fetalis, 450, 892, 893 therapy, 816 Hypsignathus montrosus, 427 T1.1/nut RNA, 776 Human herpesvirus, attachment and cell entry, 787 I Human immunodeficiency virus 1. See HIV-1 Iatrogenic infection, 150 Human immunodeficiency viruses (HIV). Iatrogenic transmission, 928 See HIV Ibaraki virus, 545 Human immunodeficiency viruses 1 and 2, 559 IBDV. See Infectious bursal disease virus Human influenza virus strains, emergence, (IBDV) 504–508 ICAM. See Intercellular adhesion molecule Human leucocyte antigens (HLA), 82 (ICAM) Human metapneumovirus, 409 ICP0, 767 diagnosis, 410 protein, 789 epidemiology, 410 ICP4 protein, 767 genome organization, 384 ICP22, 767, 800 pathogenesis, 410 ICP27, 767, 769 Human papillomavirus. See HPV ICP47, 767, 769 Human papillomavirus-16. See HPV-16 Ictalurivirus, 744 Human parainfluenza viruses, 398 Idnoreovirus, 530 Human parechoviruses, 219 IE2 protein, 770, 791 Human parvovirus B19, 876 IE63 protein, 792 Human pathogenic adenoviruses, 731–736 IEV particles, 831, 835, 843, 846 Human pathogenic anelloviruses, 910–912 IFN. See Interferons (IFN) Human pathogenic astroviruses, 234 IFN-a, 96, 102, 648 Human pathogenic bunyaviruses, 469–474 effects, 101, 102 Human pathogenic caliciviruses, 242–247 molecular properties, 97 Human pathogenic coronaviruses, 330–332 synthesis, 98 Human pathogenic flaviviruses, 269 for therapy, 112 Human pathogenic hepadnaviruses, 641–654 IFN-a receptor (IFNaR), 97, 99, 102 Human pathogenic herpesviruses, 794–817 IFN-b,96 Human pathogenic papillomaviruses. See HPV effects, 101 Human pathogenic paramyxoviruses, 398 molecular properties, 97 Human pathogenic parvoviruses, 892–898 synthesis, 98 Human pathogenic picornaviruses, 212–213 IFN-b promoter stimulator 1 (IPS-1), 99 Human pathogenic polyomaviruses, 669–673 IFN-d,97 Human pathogenic poxviruses, 846–852 IFN-e,96 Human pathogenic reoviruses, 540 IFN-g, 71, 74, 82, 103 Human pathogenic retroviruses, 598 effects, 101 Human pathogenic togaviruses, 301–306 signalling cascade, 104 Human pathogenic viruses, 150 IFN-g receptor (IFNR), 103 Human prion diseases, 30, 928–932 IFN-k,96 diagnosis, 931 IFN-l1, 103 pathogenesis, 930 IFN-l2, 103 Human rhinovirus 14, canyon structure, 193 IFN-l3, 103 Human smallpox, 829 IFN-lR, 104 Human T-lymphotropic virus 1 (HTLV-1). IFN-t,97 See HTLV-1 IFN-o,96 Index 997

IFN-z,97 Immunosensors, 180 IgA, 86, 88 piezoelectric, 181 IgD, 86, 88 IMV particles, 831, 846 IgE, 86, 88 Inactivated vaccines, 142–144 IgG, 86, 88 Inclusion bodies, 53 IgG subclasses, 88 cytoplasmic, 53 IgM, 86 negri, 53 Iinhibitors of influenza virus, 129 photographic picture, 53 Ikb,99 Indinavir, 130, 571, 609 IL-1, 96, 106 Indirect immunofluorescence tests, 177 IL-2, 106 Indirect transmission, 149 IL-3, 106 Infantile myocarditis, 217 IL-4, 106 Infantile paralysis, 213, 214 IL-5, 106 Infected cell protein (ICP), 751 IL-6, 106 Infection, 40, 46 viral, 775, 787 placenta, 46 IL-7, 106 single-phase and biphasic course, 40 IL-10, 106, 775 Infection-enhancing antibodies, 266, 585 IL-11, 106 Infectious balanoposthitis, 818 IL-12, 106 Infectious bovine rhinotracheitis, 818 IL-13, 107 Infectious bursal disease virus (IBDV), IL-15, 107 522, 526 IL-17, 107 clinical features, 527 IL-18, 107 diagnosis, 528 IL-2areceptor, 612 epidemiology and transmission, 526 IL-1 receptor associated kinases (IRAK), genome organization, 524 75, 77 pathogenesis, 528 Iltovirus, 742 Infectious canine hepatitis, 737 Imiquimod, 120, 124, 130, 703 Infectious haematopoietic necrosis of Immediate early genes, adenoviral, 715 salmonids, 369 Immediate early proteins, 767, Infectious mononucleosis, 809 769–771, 779 Infectious pancreatic necrosis virus (IPNV), Immortalized cells, 58 522, 527 Immune defence innate, 69 Infectious pustular vulvovaginitis, 818 Immune enhancement, 266 Infectious salmon anaemia virus, 21, 478, Immune escape. See Immune evasion 479, 485 Immune evasion, 92 Inflammatory chemokines, 110 Immune interferon, 103 Influenza A virus, 477–479, 481, 484–486, Immune response, adaptive, 69 489, 491, 493, 494, 498–502, 507, Immune-stimulating complexes, 142 512, 513 Immune system, 90 epidemiology, 498, 500 Immune tolerance, 6 genome organization and structure, Immunochromatography, 171 479–481 Immunofluorescence, 164, 166 genome segments, 478, 493 Immunofluorescence test, 168 haemagglutinin, 481, 484 Immunoglobulin class switch, 89 infection, 499 Immunoglobulin genes, somatic inhibitors, 128 recombination, 89 M2 protein, 486 Immunoglobulins, 86 neuraminidase, 485 classes, 86 NP protein, 512 Immunology, 69–93 NS1 protein, 489 Immunoreceptor tyrosine-based activation pandemics, 498, 499 motif, 786 particle, 480 998 Index

Influenza A virus (cont.) of viral polymerases, 118 PB1-F2 protein, 491 of viral proteases, 119 in poultry, 501, 502 of viral replication, 121–128 protein functions, 494 of virus penetration/uncoating, 128–129 reassortment, 500 In situ hybridization, 175 RNA genome segments, 481 In situ PCR, 175 structure, 479 Integrase, 591 subtype H1N1, 507 inhibitors, 609 subtypes, 500 Integration of the double-stranded DNA vaccines, 513 retroviral genome, 591 Influenza B virus, 478, 481, 485–487, 494, 498, Integrin a4b7, 585 509, 513 Integrins, 59 BM2 protein, 487 Intercellular adhesion molecule (ICAM), 585 genome segments, 478 proteins, 206 infections, 509 Intercellular adhesion molecule 1 (ICAM-1), NB protein, 486 193, 207 neuraminidase, 485 Interference, 12, 95 protein functions, 494 Interferon-a, 512 RNA genome segments, 481 Interferon regulatory factors (IRF), 75, 775 vaccines, 513 Interferons (IFN), 12–13, 92, 95–113 Influenza C virus, 478, 481, 485, 498, 506 discovery, 95 HEF protein, 485 overview, 97 reassortment, 506 type I, 96–103 RNA genome segments, 481 type II, 103 Influenza virus, 32, 481, 483, 489, 493–496, type III, 103–104 498–514. See Table 2.1 Interferon-stimulated response element among water birds, 501 (ISRE), 77, 99 antigenic shift, 503 Interleukins, 105–107 attachment and penetration, 493 Internal ribosomal entry site (IRES), attachment, 489 194, 195, 208 epidemiology and transmission, 498–508 Internal ribosomal entry site (IRES) genetic epidemiology, 503 sequences, 212 host tropism, 509–510 translation initiation, 212 immune response and diagnosis, 511–512 Interstitial cytomegalovirus pneumonia, 803 innate defence, 511 Interstitial dendritic cells, 70 neuraminidase inhibitors, 129 Intracellular enveloped viruses. See IEV nomenclature, 506 particles pathogenesis, 510–511 Intracellular mature viruses. See IMV penetration, 32 particles protein properties, 494–495 Invariant chain, 85, 584 reassortants, 151 Iodine deoxyuridine, 115 replication cycle, 496 Ion-sensitive field-effect transistors, 181 resistance against inhibitors, 131 IRES. See Internal ribosomal entry site (IRES) RNA genome segments, 481 IRF. See Interferon regulatory factors (IRF) structural proteins, 483 IRF3, 98, 535 subtypes, 506 IRF7, 98 therapy and prophylaxis, 512–514 Isaacs, A., 13, 95 zoonotic potential, 498 Isavirus, 21, 478 Influenza virus proteins, properties, 493 ISRE. See Interferon-stimulated response Inhibitors element (ISRE) non-nucleoside, 128 Iteravirus, 877 of uptake/uncoating, 120 Ivanovski, D.I., 3 of viral neuramidases, 120 Ixodes ricinus, 276 Index 999

J Lactate dehydrogenase elevating virus Jaagsiekte sheep retrovirus, 619 (LDV), 310 Jak1, 99, 102 Lactoferrin receptor, 728 Jakob, A.M., 928 Lagovirus, 236 Jaundice, 220, 253 Laidlaw, P., 6, 478, 499 JC polyomaviruses, 656, 669 Laminin 5, 692 associated diseases, 670 Lamivudine, 121, 131, 609, 649 Jenner, E., 4, 829 LAMP. See Latency-associated membrane Joest–Degen inclusion bodies, 377 protein (LAMP) Joest, E., 376 LANA. See Latency-associated nuclear antigen Junı´n virus, 438, 439, 446, 452 (LANA) Landsteiner, K., 5, 187 Langerhans cells, 42, 43, 70 K Lansbury, P., 925 Kaposins, 783, 785 Large T antigen, 661–664 Kaposi’s sarcoma, 602, 741, 755 Laryngeal papillomas, 698 Kaposi’s sarcoma-associated herpesvirus, 758 Lassa fever, 130, 151, 152, 438, 452–454 Kaufman, H.E., 13, 115 clinical features, 453 K-bZIP, 773, 793 epidemiology and transmission, 452 Keele, B.F., 600 immune response and diagnosis, 453, 454 Kemerovo virus, 545 pathogenesis, 453 Kennel cough, 411 Lassa virus, 438, 439, 446, 452, 454 Keratinocytes, 691 vaccine, 454 Keratoconjunctivitis, 115 LAT. See Latency-associated transcript (LAT) in swimming pools, 731 Latency, 36, 54 Killed vaccines, 139 Latency-associated membrane protein Killer cell immunoglobulin-like receptors (LAMP), 783, 793 (KIR), 73 Latency-associated nuclear antigen (LANA), Killing activatory receptors, 73 783, 793 KI polyomavirus, 658 Latency-associated transcript (LAT), KIR. See Killer cell immunoglobulin-like 767, 792, 807 receptors (KIR) Latent membrane proteins, of Epstein–Barr Kissing disease, 808 virus, 781–782 Kobuvirus, 18, 188, 190 LCMV. See Lymphocytic choriomeningitis Koch, R., 10 virus (LCMV) Koi herpesvirus, 741, 817 LCMV infections, 448, 450 Koplik’s spots, 403 clinical features, 450 K1 protein, 786 pathogenesis, 450 6K protein, 299 persistent, 448 KSHV-Rta, 793 L domains, of viral structural proteins, 445 Kundratitz, K., 798 LDV. See Lactate dehydrogenase elevating Kupffer cells, 70 virus (LDV) Kuroya, M., 379 Lentivirus, 557, 559, 561, 562 Kuru, 30, 920, 928 rex-dependent mRNA export, 592 clinical features, 930 tat proteins, 575 epidemiology, 928 vif protein, 581 Kyasanur forest disease virus, 276 Leporipoxvirus, 832, 842, 854 Lethality, definition, 148 Leucocyte-function-associated antigen L (LFA), 585 Laboratory methods Leukotrienes, 72 for virus detection, 163 LGP2 protein, 98 La Crosse virus, 455, 467 LHBsAg, 628, 633, 637, 638, 645, 650 1000 Index

LHDAg, 650 Machupo virus, 439, 446 Licht, C., 678 Macrophages, 42, 43, 72–73, 604 Liddington, R.C., 665 Mad Cow disease. See Bovine spongiform Lieberkuhn’s€ crypts, 336 encephalopathy (BSE) Light chain, 424 Maedi, 619 Lillie, R.D., 448 Maedi-visna virus, 12, 559, 618, 619 Lindenmann, J., 13, 95 control, 620 Line-blot tests, 177 diagnosis, 620 Lipid rafts, 38, 375, 398, 482, 537, 538 epidemiology, 618 Lipkin, W.I., 370 pathogenesis, 620 Live vaccines, 136, 139, 216 Magnus, H. von, 187 with vaccinia viruses, 141 Magnus, P. von, 112 Ljungan virus, 219 Maitland, M.C. and H.B., 7 LMP1, 61, 66, 778, 781 Major basic protein (MBP), 72 LMP2A, 772, 778, 782 Malacoherpesviridae, 741 LMP2B, 772, 778, 782 Malignant catarrhal fever, 817 Locally restricted infections, 42–43 Malignant transformation, 11, 26 Loeffler, F., 4, 187 Mamaviruses, 29 Loewenstein, E., 794 Mammary tumour virus, 561 Louping ill virus, 276, 285 Mannose-binding lectin, 334 Loviride, 119, 609 Maraviroc, 120, 609 L protein, 442, 466 Marble spleen disease virus, 738 of arenaviruses, 442 Marburgvirus, 21, 419, 426 of hantaviruses, 466 diagnosis, 430 of paramyxoviruses, 382 discovery, 426 of rhabdoviruses, 357 envelope proteins, 424 Lucke´ tumour herpesvirus, 741 epidemiology and transmission, 426 Lumpy skin disease virus, 853–854 genome, 420 Lung infections, 45 genome organization, 423 Lymphadenopathy syndrome, 602 NP protein, 423 Lymph node swelling, 43 protein functions, 422 Lymphocryptovirus, 743 symptoms, 427 Lymphocyte proliferation or stimulation test, 178 therapy, 430 Lymphocytic choriomeningitis, 6, 448 Mardivirus, 742 Lymphocytic choriomeningitis of mice, 451 Marek’s disease, 824 Lymphocytic choriomeningitis virus (LCMV), Marker vaccines, 145 152, 438, 442, 446, 448–452 Mason–Pfizer monkey virus, 561 epidemiology and transmission, 448 Mastadenovirus, 708, 709 immune response and diagnosis, 451 Mastadenovirus proteins, 724–726 replication, 442 Mast cells, 72 risk in organ transplants, 449 Maternal immunity, 90 Lymphohaematogenic dissemination, 43 Maternal passive immunity, 90 Lymphotactin, 108, 110 Maton, G. de, 301 Lymphotoxin-a, 105 Matrix proteins, 486 Lysosomes, 51, 71 retroviruses, 567 Lyssa, 362 MBP. See Major basic protein (MBP) Lyssavirus, 352, 354, 373 McCarty, M., 9 Lytic infection cycle, 36 M cells, 70 MC54L, 851 McLeod, C., 9 M MC159 protein, 851 Macaw wasting disease, 374 MC80R, 851 MacCallum, F., 12, 95 MCV-1, 851 Index 1001

MCV-2, 851 Minute virus of mice (MVM), 877, 883, 885 MCV-3, 851 genome, 880 MDA-5, 98 genome organization, 883 Measles, 379, 402 proteins functions, 884 clinical features, 402 replication, 888 inclusion body encephalitis, 405 Mizutani, S., 556 vaccine, 407 Modelling, 153 Measles virus, 379, 402 Modified vaccinia ankara (MVA) virus, associated encephalitis, 405 137, 850 attachment, 394, 404 Mokola virus, 353 epidemiology and transmission, 402 Molecular biology, emergence, 8–9 genome organization, 384 Molecular epidemiology, 153 immune response and diagnosis, 406 Molecular mimicry, 91 induction of autoimmune reactions, 90 Molluscipoxvirus, 832 pathogenesis, 403 Molluscum contagiosum virus, 851–852 prophylaxis, 407 clinical features, 851 structural and non-structural proteins, 387 epidemiology and transmission, 851 Meat and bonemeal, 940, 944, 945 genotypes, 851 scrapie and/or BSE-contaminated, 940 pathogenesis, 851 Mechanisms of antigen processing, 85 Monkeypox virus, 847 Medin, O., 187 Monocyte colony-stimulating factor, 73 Meister, J., 362 Monocytes, 72–73 Melnick, J., 656 Mononegavirales, 351 Menangle virus, 417 Mononucleosis, 91, 808 Meningoencephalitis, 47, 255 Montagnier, L., 556, 598 Merkel cell carcinoma, 58, 673 Morbidity, definition, 148 Merkel cell polyomavirus, 58, 658, 672–673 Morbilliviruses Merkel cell polyomavirus DNA, 657 F protein, 386 Meselson, M., 9 H protein, 386 Metapneumovirus, 381 Morphogenesis, 37 Metastasis, 60 Mortality, definition, 148 Mexican flu, 505–507 Mouse hepatitis virus, 318, 321, 335 MHBsAg, 628, 638, 645, 650 attachment, 328 MHC antigens, 45 Mouse mammary tumour virus, 556, 565 reduction by viruses, 92 Mousepox virus, 852 MHC class I antigen, 80, 81, 584 M protein, 323, 325 loading, 85 of coronaviruses, 327 structure, 83 of paramyxoviruses, 390, 398 MHC class II antigen, 82, 84–85 of rhabdoviruses, 358 loading, 85 M1 protein, 480, 486 MHC class I proteins, 73 influenza A virus, 480 loading, 80 M2 protein, 479 MHC class II proteins, 70, 73 M2-1 protein, 383 Microfilaments, 59 Mucine-like domains, 424 b2-Microglobulin, 81 Mucin-like protein domains, 429 Microtus arvalis, 470 Mucin-like proteins, 429 Middle T antigen, 664 Mucins, 429, 509 Midges, 547 Mucosal disease, 289 Mimicking viruses, 29 Muerhoff, S., 282 Mimiviruses, 28–29 Multicentric castleman’s disease, 741 Minichromosome maintenance element, 693 Multiplex PCR, 175, 180 Mink enteritis virus, 877, 898 Mumps, 379, 401 Minks, 938 Mumps virus, 46, 381, 400 1002 Index

Mumps virus (cont.) Negative marker vaccines, 145 clinical features, 400 Negative-sense, 437 epidemiology and transmission, 400 Negative-sense RNA viruses, 34–35 genome, 382 Negri, A., 7, 367 genome organization, 383, 384 Negri inclusion bodies, 53, 367 immune response and diagnosis, 401 Nelfinavir, 609 pathogenesis, 401 Nelvinavir, 119 prophylaxis, 401 NendoU, 312, 313 structural and non-structural proteins, 387 Neo-cannibalism, 939, 942 Munch,€ J., 599 Neotma, 453 Munk, K., 794 Nested PCR, 173 Mupapillomavirus, 679 Neural cell adhesion molecule, 359 Murine leukaemia virus, 6 Neuraminidase (NA), 129, 485 Murine polyomavirus, genome organization, crystallographic structure, 485 659 of influenza A viruses, 485 Muromegalovirus, 743 Neurogenic dissemination, 43–44 Mus musculus, 438 Neutrophils, 71, 110 MxA proteins, 102 Nevirapine, 119, 123, 128, 609 Mx proteins, 102, 104, 511 Newcastle disease virus, 411 Mycoreovirus, 530 attachment, 394 Myeloid dendritic cells, 70 clinical features, 411 Myeloid differentiation primary response epidemiology and transmission, 411 gene 88 (MyD88), 74 immune evasion, 393 Myeloid stem cells, 73 pathogenesis, 411 Myocarditis, 46 New flu, 505–507 Myonycteris torquata, 427 New influenza virus, 507 Myxoma virus, 160, 854–855 New World arenaviruses, 439, 446 for biological control of rabbit pest, 854 NFX1-91, 688 clinical features, 854–855 Nidovirales, 309, 318 transmission, 854 Nipah virus, 160, 381, 417, 418 attachment, 394 pathogenesis, 418 N NK cells. See Natural killer (NK) cells N-acetylneuraminic acid, 488 Non-A, Non-B hepatitis viruses, 257 Nahmias, A., 794 Non-nucleoside inhibitors, 128, 609 Nairobi sheep disease virus, 474, 476–477 Non-nucleoside inhibitors of reverse clinical features, 477 transcriptase, 121 diagnosis, 477 Non-paralytic poliovirus infections, 214 epidemiology and transmission, 476–477 Non-structural proteins, 467 Nairovirus, 458, 463 of astroviruses, 232 G protein, 463 of bunyaviruses, 467 NA proteins, 486 of caliciviruses, 238–240 of influenza A viruses, 486 of coronaviruses, 323 influenza viruses, 486 of flaviviruses, 263–265 Nasopharyngeal carcinoma, 741, 808, 810 of herpesviruses, 763–775 Natural killer (NK) cells, 73 of paramyxoviruses, 391 NB protein, 486 Norovirus (Norwalk virus), 18, 41, 236, 239, influenza B viruses, 486 242–247 Necrosis, 49–51 clinical features, 243 Nefilnavir, 130 diagnosis, 243 Nef protein, 583, 594 entry gates, 41 functions, 583 epidemiology and transmission, 242 Negative elongation factor (NELF), 651 genome organization, 238, 239 Index 1003

pathogenesis, 243 Okazaki fragments, 36 replication, 241 Old dog encephalitis, 414 viral proteins, 238 Oldstone, M.B.A., 448 zoonotic transmissions, 242 Old World arenaviruses, 446 Northern blot, 168 Oncogenes, 57, 556, 557, 596, 614 Nosocomial infection, 150 cellular, 578 Novel retrovirus types, 596 Oncogenic human papillomavirus vaccines, Novirhabdovirus, 352, 373 143 NP protein of orthomyxoviruses, 487, 495 Oncogenic retroviruses, 11, 57, 158 Npro protein, 265 Oncornaviruses, 556 N protein, 465 O’nyong-nyong virus, 293 of coronaviruses, 328 Ophtalmic zoster, 799 of hantaviruses, 465 Oral polio vaccine, 216 of paramyxoviruses, 383, 390 Orbivirus, 529, 534, 545 of rhabdoviruses, 356 Orf virus, 855 NS2/NEP protein, 497 Ornithodoros, 860 orthomyxoviruses, 497 Orphan virus, 187 NSP1, 296 Orthobunyavirus, 457, 463 of arteriviruses, 312 natural hosts, 457–458 NSP1a, 232 Orthohepadnavirus, 627 NSP1ab, 232 glycoproteins, 634 NSP1b, 231 X protein, 636 NSP2, 296 Orthomyxoviridae, 21, 437 NSP3, 296 Orthomyxovirus, 34, 477–514 NSP4, 296 attachment, 493 of arteriviruses, 312 characteristic prototypes, 478 NSP11, of arteriviruses, 312 characteristic representatives, 479 NS1 protein, 489–491, 497 classification, 478 influenza viruses, 489 structure, 479 orthomyxoviruses, 497 Orthopoxvirus, 830, 832, 847, 852 respiratory syncytial virus, 391 Orthoreovirus, 22, 529, 539 NS2 protein, respiratory syncytial virus, 391 Orthoretrovirinae, 557, 558 NSs protein, 467 Oryzavirus, 530 of orthobunyaviruses, 467 Oscillating quartz crystals, 180 phleboviruses, 467 Oseltamivir, 120, 129, 513 Nuclear factor kB (NFkB), 54, 61, 75, 99, Osteopetrosis, 614 565, 612 OTU proteases, 466 Nucleic acids detection, 168 Outbreak-control vaccination, 136, 150, 513 Nucleocapsid, 27 Ovine pulmonary adenocarcinoma, 619 of paramyxoviruses, 381 proteins of filoviruses, 420 proteins, retroviruses, 567 P Nucleolin, 207, 889 p17, 587 Nucleoprotein, of arenaviruses, 443 p53, 717 Nucleorhabdovirus, 373 gene, 63 Nucleoside analogue, 121–127, 609, 765 molecular effects, 717 Nupapillomavirus, 679 protein, 63–65 p130, 716 p150, 297 O Pandemic, def, 148 Oct-1, 763 Pandemic influenza A (H1N1) 2009, 507 Oct-2, 763, 791 Panencephalitis, sclerosing, 12 Ohomyxoviruses, replication, 495 Papillomas, 678 1004 Index

Papillomaviridae, 23, 626 particle structure, 382 Papillomavirus, 6, 11, 55, 62, 678–705 penetration, 33 animal pathogenic, 704–705 protein interactions model, 396 animal transmission, 704 replication, 394 attachment, 692 structural and envelope proteins, 385 characteristic prototypes, 679–680 structure, 381 classification, 678 viral proteins, 385 clinical features, 696 Parapoxvirus, 832, 849 cofactors involved in carcinogenesis, 699 electron micrograph, 835 differentiation dependent gene expression, Parechovirus(es), 187, 188, 190, 694 206, 219 early proteins, 686 clinical features, 217 electron micrograph, 682 epidemiology and transmission, 216 epidemiology and transmission, 695–696 Parvoviridae, 25, 876 evasion of the immune response, 66, 92 Parvovirinae, 876 genome organization and structure, 683 Parvovirus, 32, 62, 876–904 genome structure, 684 animal pathogenic, 898–904 immune response and diagnosis, 702–703 canine, 898, 903 L1 and L2 proteins, 691 characteristic prototypes, 877 late proteins, 691 classification, 876 pathogenesis, 699 electron micrograph, 876 proteins, 685 feline and canine, 898–901 replication, 692 feline transmission, 898 structure, 682 functions of proteins, 884 viral proteins, 683 genome, 878 Papovaviridae, 656 genome replication model, 891 Paque test, 8 human pathogenic, 892–898 Parainfluenza virus 1, tructural and non-structural proteins, 885 non-structural proteins, 387 porcine, 877, 901–902 Parainfluenza viruses, 44, 394, 398 replication, 888 attachment, 394 structural proteins, 883 clinical features, 398 structure, 878 epidemiology, 398 viral proteins, 883 immune response and diagnosis, 399 Parvovirus 4, 897 pathogenesis, 399 Parvovirus-associated arthritis, 893 Paralytic, poliovirus infection, 214 Parvovirus-associated replication bodies, 888 Paramyxoviridae, 20, 379 Parvovirus B19, 55, 885–886, 892–895 Paramyxovirinae, 380 clinical features, 893 Paramyxoviruses, 33, 34, 379, 495, 511 diagnosis, 895 animal pathogenic, 411 epidemiology and transmission, 892 attachment, 394 genome, 878 classification and characteristic prototypes, genome organization, 883 380 genome structure, 880 evasion of interferon-mediated defence infection during pregnancy, 893 responses, 393 non-structural proteins, 885 F protein, 386, 389 NS1 protein, 886 functions of proteins, 387 particle structure (schematic depiction), genome organization and structure, 382 879 genome replication, 396 pathogenesis, 893 human pathogenic, 398 persistent infection, 894 L protein, 390 proteins functions, 884 non-structural proteins, 391 replication, 888–892 nucleocapsid proteins, 390 structural proteins, 883 Index 1005

therapy, 895 discovery, 187 time course of the disease, 895 entry gates, 41 Passive vaccination, 135 enzymes, 202 Pasteur, L., 3, 4, 361 evolution, 157 Pathogen-associated molecular patterns, 74 genome comparison, 194 Pathogenesis, 39 genome organization and structure, 194 Pathogenicity, definition, 40 genome replication, 210 Pathways for spread of viruses, 42–47 human pathogenic, 212 Pattern recognition receptor family, 70 particle structure, 193 Pattern-recognition receptors, 74 polyprotein, 197 PB1-F2 protein, 491 proteases, 202 PB1 protein of orthomyxoviruses, 488 replication, 205 PB2 protein, 488, 497 RNA-dependent RNA polymerase, 203 orthomyxoviruses, 488 structural proteins, 200 of orthomyxoviruses, 488, 497 structure, 191 PDZ domains, 688 viral protein, 195 Penetration, 32 PKR. See Protein kinase R (PKR) Pentons, 710 Placenta Peptide vaccines, 143–144 infection, 46 Peptidomimetics, 128, 130 types, 90 Peramivir, 120 Plant pathogenic viroids, 651 Perforins, 82 Plasmacytoid (lymphoid) dendritic cells, 70 Permeability transition pore complex, 491 Platelet-derived growth factor, 60 Peromyscus maniculatus, 470 Pleconaril, 120, 124, 128 Persistent infections, 39 PL1pro, 323, 329 Peste-des-petits-ruminants virus, 412 PL2pro, 323, 329 Pestivirus(es), 19, 255, 285 Pneumovirinae, 380 7 kD protein, 264 Pocket factor, 201 7k protein, 299 Pol, 562 polyproteins, 258 Pol gene, 570 Peters, D., 426 Poliomyelitis, 7, 47, 212–215 Peyer patches, 42 virus transmission, 152 Peyer plaques, 215 Polio vaccines Pfeiffer, E., 809 contaminated with SV40, 675–676 Phagocytes, 43, 72 SV40 contamination, 674 Phleboviruses, 457, 464, 467, 468 Poliovirus(es), 18, 32, 47, 150, 189, 205, 213 non-structural proteins, 467 capsid proteins, 193 replication, 468 clinical features, 214 Phocine distemper, 415 epidemiology and transmission, 213 Phocine distemper virus, 380 immune response and diagnosis, 215 Phocine distemper virus 1, 415 pathogenesis, 215 Phocine distemper virus 2, 415 therapy and prophylaxis, 216 Phocoena spinipinnis papillomavirus, 682 types, 213 Phosphatidylinositol 3-hydroxykinase, 729 vaccine, 216 Phytoreovirus, 530 Poliovirus 1, genome structure, 194, 195 Picornaviridae, 18, 186, 188 Poliovirus infection Picornavirus(es), 41, 51, 187–188 non-paralytic, 214 cellular receptors, 206 paralytic, 214 characteristic prototypes, 189–190 Polykaryocytes, 53 classification and characteristic Polymerase chain reaction (PCR), 172 prototypes, 188 multiplex, 180 3CLpro, 323 nested, 173 comparison of proteins, 198–199 principle, 174 1006 Index

Polyoma, 656 Porcine transmissible gastroenteritis virus, Polyomaviridae, 23, 626, 656 336–337 Polyomavirus, 656–676 clinical features, 336 animal pathogenic, 673 epidemiology and transmission, 336 attachment and penetration, 666 pathogenesis, 336 characteristic prototypes, 657 Positive marker vaccines, 145 classification and characteristic Positive-sense RNA viruses, 34 prototypes, 656 Postexposure prophylaxis, 368 clinical features, 669–670 Postexposure vaccination, 368 epidemiology and transmission, 669 Post-polio syndrome, 214 genome organization and Post-transcriptional regulatory structure, 658 element, 632 genome replication, 667 Post-transcriptional transactivators, human pathogenic, 669–673 retroviruses, 578 immune response and diagnosis, 672 Post-transplant lymphoproliferative non-structural proteins, 665 disorder, 809 pathogenesis, 670 POU, 763 protein functions, 662 Poultry enteritis mortality syndrome, 235 replication, 665 Poxviridae, 24, 626, 829 structural proteins, 665 Poxviruses, 33, 36, 52, 93, 829–855 structure, 657 accessory proteins, 838–842 therapy, 673 animal pathogenic, 852–855 viral proteins, 660 attachment and penetration, 842 Polyomavirus-associated nephropathy, 669 characteristic prototypes, 832–833 Popper, E., 5, 187 classification and characteristic prototypes, Porcine circoviruses (PCV–1), 905, 913–914. 830–831 See also Porcine circoviruses (PCV) enzymes, 835–838 vaccines genome, 833–835 Porcine circoviruses–2 (PCV–2), 905, 913 genome structure, 836 clinical features, 913 infection cycle, 843 diagnosis, 914 of insects, 832 pathogenesis, 913–914 intermediate genes, 845 Porcine circoviruses (PCV) vaccines, 914 replication, 842–846 Porcine haemagglutinating encephalomyelitis sagittal section, 835 virus, 335 structural proteins, 835 Porcine herpesvirus structure, 832 clinical features, 820 uracil-DNA glycosylase, 838 control, 821 of vertebrates, 832 diagnosis, 821 viral proteins, 835–842 pathogenesis, 821 Poxvirus particle transmission, 820 cross-section, 834 Porcine herpesvirus 1, 820–821 structure, 834 Porcine parvovirus, 877, 901–902 pp65, 762 Porcine postweaning multisystemic wasting P protein syndrome (PMWS), 913 complexes, orthomyxoviruses, 488 Porcine reproductive and respiratory syndrome of rhabdoviruses, 357 virus (PRRSV), 316–317 of rubulaviruses, 392 clinical features, 317 Pre-B cells, 89 control and prophylaxis, 317 Preintegration complex, 591 epidemiology and transmission, 316 Primary effusion (body-cavity-based) structure, 311 lymphoma, 741, 782 Porcine rotavirus, 533 Primary liver cell carcinoma, 645–647 Porcine teschoviruses, 224 Primary viraemia, 43 Index 1007

Prion conversion, 29 Q Prion diseases, 919, 921 Quasispecies, 130, 156, 597 in animals, 932–946 Quil-A, 142 classification and characteristic prototypes, 920 forms and manifestations, 921 R Prion propagation, 925 Rabbit calicivirus, 247 Prion protein (PrP), 92 Rabbit haemorrhagic disease virus (RHDV), structure, 922 160, 236, 240, 246–247 Prions, 29–30, 919–946 for biological control, 247 PRNP, 922 clinical features, 247 Prnp gene, 935 diagnosis, 247 Progressive multifocal leucoencephalopathy, 12 epidemiology and transmission, 246 Proinflammatory cytokines, 70 genome organization, 239 Prospect Hill virus, 463 pathogenesis, 247 Protease Clara, 483 prophylaxis, 247 Protease inhibitors, 609 Rabbit myxomatosis, 855 Protease, retroviral, 571 Rabbit myxoma virus, 5 Protein, 851 Rabies, 361, 362 Proteinaceous infectious particle, 29, 920 first vaccines, 362 Protein detection, 165 history, 361 Protein kinase R (PKR), 101, 490 transmission by organ transplants, 363 Protein-only hypothesis, 920 untreated, 365 Protein p53, 63 vaccination, 368 Proto-oncogene, 617, 646 vaccination of foxes, 368 Proventricular dilatation syndrome, 31 vaccination of raccoons and foxes, 142 Provirus, 11 Rabies virus, 5, 20, 41, 43, 47, 352, 359, 362 Provost, P., 219 clinical features, 364 PrPC, 29, 922 entry gates, 41 PrPC and PrPSc, 927 epidemiology and transmission, 362 cell biology of conformational conversion, G protein, 366 927 immune response and diagnosis, 367 distinction, 932 pathogenesis, 365 PrPC into PrPSc, conformational conversion proteins, 356 model, 925 replication, 359 PrP coding gene structure, 922 strain PV, 355 PrP gene structure, 924 therapy and prophylaxis, 368 PrP isoforms structure, 924 Rabies virus infection, in transplant PrPSc, 29, 922, 930, 940, 945 recipients, 363 detection, 945 Raltegravir, 609 plaques, 930 Raoult, D., 29 PRRSV. See Porcine reproductive RB. See Retinoblastoma proteins (RB) and respiratory syndrome virus RB105, 65, 663, 689, 716 (PRRSV) function, 690 Prusiner, S.B., 920 tumour suppressor protein, 612 Pseudocroup, 379 RB107, 65, 689, 716 Pteropus sp., 418 RBP-Jk, 780 Pu-1, 780 Real-time PCR, 173 Pulvertaft, R., 808 Reassortants, 437 pU94 protein, 771 Reassortment, 500 Purtilo, D., 809 Receptor-mediated endocytosis, 32 Puumala virus, 455, 470 Recombinant viruses, 141–142 pVP87, 232, 233 Reed, W., 5, 270 1008 Index

Re-emerging viruses, 151 genome organization and structure, 561 Regulator of expression of virion proteins. human pathogenic, 598 See REV protein inhibitors, 128 Regulatory T cells, 80, 85–86 integrase, 572, 591 Reoviridae, 22, 521, 529 leader region, 564 Reoviruses, 35, 528–551 LTR region and promoter, 565 animal pathogenic, 545 oncogenic, 57, 158 attachment and penetration, 538 polypurine tract, 565 characteristic prototypes, 530 replication, 585 epidemiology and transmission, 540 reverse transcriptase, 571 genome, 531 reverse transcriptase inhibitors, 126 human pathogenic, 540 structure, 560 non-structural proteins, 535 variability, 572, 597 reassortants, 540 viral proteins, 567 replication, 538 Reverse genetics, 144 structure, 529 Reverse transcriptase, 35, 556, 571 Rep68, 883, 886, 887 discovery, 11 Rep78, 883, 886, 887 inhibitors, 609 Replication of togaviruses, 300–301 non-nucleoside inhibitors, 121 Rep proteins, 886 Reverse transcriptase activity determination, Resistance tests, 180 166 Respiratory enteric orphan virus. See Reverse transcription, 596 Reoviruses Rev protein, 578, 594 Respiratory syncytial virus, 44, 54, 379, Rev response element (RRE), 579 394, 407 Rex-dependent mRNA export, 592 bovine, 416 Rex proteins, 581, 595 clinical features, 408 Rex response element (RxRE), 581 epidemiology and transmission, 407 Reye syndrome, 509 genome organization, 384 Rey, F.A., 261 M2-1 protein, 390 RGD motif, 729 pathogenesis, 408 Rhabdoviridae, 20, 352 structural and non-structural proteins, 387 Rhabdoviruses, 34, 352 therapy, 409 animal pathogenic, 368 Respirovirus characteristic prototypes, 353 HN protein, 386 classification, 352 structure, 382 genome organization and structure, 355 Reston ebolavirus, 420 genome replication, 360 Reticular endocytic system, 43 G protein, 354 Reticulohistiocytic system, 43 human and animal pathogenic, 362 Retinoblastoma gene, 65 replication, 358 Retinoblastoma proteins (RB), 64–65 structure, 354 Retinoic acid inducible gene (RIG–1), 98 Rhadinovirus, 743, 758 Retroviral vectors, 597 RHDV. See Rabbit haemorrhagic disease virus Retroviridae, 22, 557 (RHDV) carcinogenesis, 57 Rhinovirus(es), 32, 44, 223–224 Retroviruses, 35, 555, 567 cellular receptors, 206 animal pathogenic, 613 clinical features, 223 characteristic prototypes, 558 epidemiology and transmission, 223 classification and characteristic prototypes, immune response and diagnosis, 224 557 pathogenesis, 223 emergence of novel retroviruses, 596 serotypes, 202 endogenous, 557 therapy and prophylaxis, 224 exogenous, 557 Rhipicephalus appendiculatus, 476 Index 1009

Ribavirin, 120, 129 non-structural proteins, 535 Ribozymes, 132 NSP1 protein, 535 Rift valley fever virus, 463, 474–476 NSP2 protein, 535 clinical features, 475 NSP3 protein, 535 diagnosis, 476 NSP4 protein, 536 envelope proteins, 463 NSP5 protein, 537 epidemiology and transmission, 475 NSP6 protein, 537 pathogenesis, 476 outer capsid, 533 (RIG-I)-like helicases (RLH), 98 particle structure, 531 Rimantadine, 120, 128, 512 pathogenesis, 543 Rinderpest virus, 379, 382, 402, 403, 412 reassortants, 542 control and prophylaxis, 413 structure, 529 diagnosis, 413 therapy and prophylaxis, 544 epidemiology and transmission, 412 vaccine, 544 pathogenesis, 413 viral core, 534 Ritonavir, 119, 130 Rous, P., 5, 57, 556 River, C., 10 Rous sarcoma virus, 5, 57, 556, 613 Rizzetto, M., 649 Rowe, W.P., 8, 708 RNA-dependent RNA polymerase, 34, 35, 186, Rta, 772 203, 443–444 Rubella of arenaviruses, 443–444 embryopathy, 302 RNA-induced silencing complex (RISC), 727 postnatal, 304 RNA interference, 132 prenatal, 305 RNA polymerase II, 594, 597 syndrome, 302 error-prone, 597 Rubella virus, 293, 294, 301 RNA splicing, 9 clinical features, 303 discovery, 708, 710 epidemiology and transmission, 302 RNA virus capsid (RVC) domain, 193, 200 E1 protein, 299 RNA viruses, 33–35 E2 protein, 299 double-stranded, 35 genome organization, 294, 295 evasion of immune defence, 92 immune response and diagnosis, 304 mutations, 156 non-structural proteins, 297 negative sense, 34 pathogenesis, 303 positive-sense, 34 prenatal infections, 303 Robbins, F.C., 187 replication, 300 Rolling-circle replication, 36 structural proteins, 298 Roniviridae, 318 structure, 294 Roseola infantum, 806 therapy and prophylaxis, 305 Roseolovirus, 743 time course of antibody formation, 303 Rossmann, M., 201 Rubivirus(es), 292, 293, 297–298 Ross River virus, 293 Rubula virus, 380, 393 Rotaviruses, 41, 529–531, 540, 545 HN protein, 386 clinical features, 542 68 rule, 505 entry gates, 41 Russian flu, 500, 504, 512 failure in developing vaccines, 544 RVC. See RNA virus capsid (RVC) domain functional domains of NSP4, 536 R5 virus, 574, 586, 601, 604 genome, 531 RxRE sequences, 581 genome segments, 532 haemagglutination activity, 533 immune response and diagnosis, 543 S infections, 529 Sabia´ virus, 439, 446 inner capsid, 534 Sabin, A.B., 8, 216, 273 nomenclature, 542 Sachs, L., 11 1010 Index

Saimiriine herpesvirus, 758 Serum response elements, 61 Salahuddin, S.Z., 806 Severe acute respiratory syndrome (SARS), Salk, J.E., 8 14, 152, 159, 330, 332, 333 Salk vaccine, 675 SEVI proteins, 599 Sapovirus(es), 236, 237, 242–247 SFV. See Simian foamy virus (SFV) clinical features, 243 Sharp, P.A., 710 diagnosis, 243 SHBsAg, 628, 638, 649, 650 epidemiology and transmission, 242 SHDAg, 650 genome organization, 238, 239 Sheeppox virus, 853–854 pathogenesis, 243 Shingles, 603, 798, 799, 801 replication, 241 Shipping fever, 411 viral proteins, 240 Shipyard eye, 735 SAP proteins, 809 (Shope) cottontail rabbit papillomavirus, 678 Saquinavir, 119, 130, 571, 609 Shope rabbit papillomavirus, 699 SARS. See Severe acute respiratory syndrome Shope, R.E., 6, 11, 478, 678 (SARS) SH protein, 391 SARS-related coronavirus, 151, 318, 332–335 Siadenovirus, 709 attachment and penetration, 328 Sialic acid, 483 clinical features, 333 Sialomucins, 429 control, 335 Siegert, R., 426 epidemiology and transmission, 332 Sigma replication, 36 genome organization, 321 Signal peptides, 445 genome organization and replication, 322 Signal recognition particle, 268 immune response and diagnosis, 335 Signal transducer and activator of transcription pathogenesis, 334 (STAT), 99 replication, 328 Sigurdsson, B., 12, 618 Satellite viruses, 28–29 Simian foamy virus (SFV), 559, 560, 569 Schaefer, W., 478 genome structure, 564 Schlesinger, R.W., 273 LTR region, 566 Schneweis, K., 794 protein properties, 569 Schramm, G., 9 Simian haemorrhagic fever virus, 310 Sclerosing panencephalitis, 12 Simian immunodeficiency virus (SIV), 159, Scrapie, 30, 919, 933–936 559, 598 atypical, 934, 935 Nef protein, 583 clinical features, 934 vpu protein, 582 control, 936 Simian virus 40, 674–676. See also SV40 diagnosis, 936 Simplex virus type 1, 768 epidemiology and transmission, 933 Sindbis virus, 158, 293, 294, 299 pathogenesis, 935 attachment and penetration, 300 Scrapie-associated fibrils, 924 genome organization, 295 Seadornavirus, 530 pathogenicity, 307 Secondary viraemia, 43 Single-stranded DNA viruses, 37 Self-assembly, 37 Sin Nombre virus, 458, 470 Semen-derived enhancer of viral infection, SIVcpz, 159, 598 SEVI, 599 SIVmac, 599 Semliki forest virus, 293, 294, 296, 307 SIVmac239, 583 Sendai virus, 379 SIVsmm, 599 attachment, 394 Sixth disease, 806 non-structural proteins, 392 Skehel, J., 488 Sentinel cells, 70 Slenczka, W., 426 Seoul virus, 458 Slow viral infections, 12 Sergeant, 892 Small interfering RNA, 132 Serpins, 841 Smallpox, 4, 829, 846 Index 1011

Smallpox vaccination, 830, 850 of paramyxoviruses, 385 Small T antigen, 664 of parvoviruses, 883–885 Smear infections, 149 of picornaviruses, 197–202 Smith, W., 6, 478, 499 Subacute sclerosing panencephalitis, 405 Snowshoe hare virus, 457, 474 Subtilisin-like proteases, 482 Sodium dodecyl sulphate-polyacrylamide Subunit vaccine, 143 gel, 165 Sudan ebolavirus, 426 Sodroski, J., 574 Suid herpesvirus 1, 820–821 Sorting signals, 445 Suipoxvirus, 832 Southern blot, 168 Summer flu, 217 principle, 169 Superantigens, 91 Spanish flu, 7, 157, 478, 499, 505 SV40, 58, 62, 656 Spikes, 479 clinical features, 674–675 Spring viraemia of carp, 369 derived vectors, 668–669 S protein of coronaviruses, 323 diagnosis, 676 Spumaretrovirinae, 557 epidemiology and transmission, 674 Spumaretrovirus, 559 genome organization, 659 Spumavirus, 155, 557, 559, 572 large T antigen, 661 Sputnikvirus, 29 model system for molecular biology, 660 Squamous cell carcinoma, 699 pathogenesis, 675 Squirrels, 474 sequence elements in the regulatory Src kinase, 782 region, 661 Staggering disease, 376 small T antigen, 664 Stahl, F.W., 9 structure, 658 Stanley, W., 8 Swamp fever, 620 Staphylococcus aureus, 493 Sweet, B., 656, 675 STAT. See Signal transducer and activator of Swine flu, 151, 505–507 transcription (STAT) Swine influenza, 478 STAT1, 99 Swinepox, 850 STAT2, 99 Swine vesicular disease virus, 188, 224 STAT3, 99 Syk kinases, 782 STAT5, 99 Sylvatic or wild rabies, 362 State of latency, 26 Symmetry forms of viral capsids, 27 Stavudine, 119, 121 Syncytia, 53 Stehelin, D., 556 Syncytia formation, 53–54, 407 Steiner, R., 798 Syndesmochorial placenta, 90 Stewart, S., 656 Stick tests, 170 Stillbirth, mummification, embryonic death T and infertility (SMEDI), 901 T20, 609 St. Louis encephalitis virus, 255 Tacaribe virus, 439 Stoddard, M.B., 798 Talfan virus, 225 Straus, S.E., 798 Tanapox virus, 847 Streptococcus pneumoniae, 493 TANK, 99 Stromal cell derived factor 1, 586 T antigen, 660 Structural proteins, 460, 463, 465, 481–489 Taq polymerase, 172 of astroviruses, 232 TAR element, 577 of bunyaviruses, 460, 463, 465 Targeted empiricism, def, 13 of caliciviruses, 240–241 TAR-RNA-binding protein (TRP) 1 of coronaviruses, 323–328 complex, 576 of flaviviruses, 260–263 Tas protein, 578 of herpesviruses, 747–750, 758–763 Tat-binding cellular proteins (TBP), 576 of influenzaviruses, 481–489 Tat protein, 567, 575, 594 1012 Index

Tax protein, 61, 567, 578 TIR-domain-containing adapter inducing Tax response elements (TREs), 567 IFN-b (TRIF), 75 TBEV. See Tick-borne encephalitis virus TLR. See Toll-like receptors (TLR) (TBEV) TLR1, 74 T-cell leukaemia, 556 TLR2, 74 T-cell receptor (TCR), 79, 82 TLR3, 74 diversity, 79 TLR4, 74 T cells TLR5, 74 co-stimulatory signals, 80 TLR6, 74 regulatory, 85 TLR7, 74 gd T cells, 79 TLR8, 74 Tegument layer, 28 TLR9, 74 Telaprevir, 120 TLR11, 74 Telbivudine, 649 TLRs, 74 Temin, H., 11, 556 T lymphocytes, 79 Teravirus, 877 TNF. See Tumour necrosis factors (TNF) Teschovirus, 190 TNF-a, 105 Tetherin, 582 TNF-a converting enzyme, 105 Tetramer test, 178 TNF-b, 105 sequence of the test procedure, 179 TNF receptor, 105 Tev protein, 594 TNF-receptor-associated factor (TRAF) 3, 99 TGF. See Transforming growth factor (TGF) Tobacco mosaic virus, 8 TGF-a, 61, 111 Togaviridae, 19, 186, 292 TGF-b, 60, 111 Togavirus(es), 290–309 TH cells, 84–85 animal pathogenic, 306–309 TH1 cells, 85 capsid protein, 298 TH2 cells, 85 characteristic prototypes, 293 Theiler, M., 272 classification and characteristic T-helper cells, 82 prototypes, 292 Therapy and prophylaxis togoviruses, 305 genome, 294 Thogoto virus, 478, 511 genome organization and replication, 295 Three day fever, 806 human pathogenic, 301–306 Thymidine analogue, 121 non-structural proteins, 294, 296 Thymidine kinase, 764, 765 polyprotein, 298 Thymidylate synthase, 764 protein functions, 300 Tick bites, 276 structure, 294 Tick-borne encephalitis virus (TBEV), 19, 151, viral proteins, 296 255, 257, 276–278 Toll/IL-1 receptor (TIR) domain attachment, 266 proteins, 74 clinical features, 276 Toll-like receptors (TLR), 74 epidemiology and transmission, 276 TLR-mediated activation E protein, 277 pathways, 76 E protein structure, 263 Toll-like receptors 7 and 8, 511 genome organization, 262 ligand, 511 immune response and diagnosis, 277 Torovirinae, 319 life cycle, 267 Torovirus, 319 particle structure, 257 Torque teno virus, 875, 905, 906, pathogenesis, 277 910–912 structure of the E protein, 261 clinical features, 911 therapy and prophylaxis, 278 diagnosis, 911 a-TIF protein, 761 epidemiology and transmission, Tiger heart, 227 910–911 Tiny T antigen, 660, 664 genome organization, 908 Index 1013

genotypes, 910 V pathogenesis, 911 Vaccination, 4, 142 replication, 909, 911 active, 135 TRAF-1, 781 ancient, 4 TRAF-2, 782 passive, 135 TRAF-family-associated NFkb activator, 99 against rabies, 136 Transactivators, retroviral, 575 Vaccines, 135–145, 216, 513 Transformation, 11, 57–67 against classical swine fever virus, 137 Transformed cells, 59 development, 137 cell growth changes, 60 DNA, 144 evasion of the immune response, 66 against influenza, 513 morphological changes, 58–62 marker, 145 Transforming growth factor (TGF), 60, 111 overview, 139 Transmissible mink encephalopathy (TME), against papillomaviruses, 143 921, 938 peptide, 143 Transmissible spongiform encephalopathies using selected proteins, 143 (TSEs), 919 Vaccinia virus, 141, 829–832, 842, 849 Transport-associated protein, 82 Ankara, 831 Traub, E., 6, 448 attenuation, 137 Trentin, J.J., 708 enzymes, 839–840 Tropical spastic paraparesis (TSP), 611 as expression system in genetic TT virus, 905 engineering, 830–831 Tula virus, 463, 470 genome structure, 836 Tumour necrosis factors (TNF), 96, 105–108 recombinant, 850 Tumour-suppressor protein, 690 structural proteins, 837–838 inactivation, 62–63 vaccine, 850 p53, 63, 688 Vaccinia virus early transcription factor Tumour suppressors, 62 (VETF), 844 Tumour viruses, 58 Valovirus, 236, 237 evasion of the immune defence, 66 Variant CJD, 929 Twort, F., 5 clinical features, 930 Tyk2, 99, 102, 701 Variant Creutzfeldt–Jakob disease, 30 Type I interferons, 96 Varicella-zoster virus, 24, 40, 43, 741, effects, 99 756–757, 759, 784, 798–801 Type III interferons, 103 clinical features, 799 Tyrrell, D.A.J., 318 epidemiology and transmission, 798 genome, 756 genome structure, 753 U latent infection cycle, 792 UL18, 804 pathogenesis, 800 UL80a, 751 reactivation, 799 Ultraviolet-damaged DNA-binding protein, structural proteins, 760 636 therapy, 801 Uncoating, 33 vaccination, 801 Uracil DNA glycosylase, 766, 838 Varicellovirus, 742 Uracil glycosylase, 764 Variola minor, 846 Urbani, C., 332, 333 Variolation, 4, 829 Urban rabies, 362 Variola vera, 829, 846 US6, 774, 805 Variola virus, 832, 846–850 US11, 805 clinical features, 848 US11, 762 epidemiology and transmission, 846–848 US28, 805 pathogenesis, 848–849 Uukuniemi virus, 463 Variot, G., 678 1014 Index

Varmus, H.E., 556 Viral IRF-3 (vIRF-3), 775 Vascular endothelial growth factor, 848 Viral IRF1-IRF4, 783 VDAC1. See Voltage-dependent anion channel Viral morphogenesis, 37 1 (VDAC1) Viral neuraminidases inhibitors, 120 Vectors derived from BPV-1, 695 Viral nucleic acids detection, 168 Venezuelan equine encephalitis virus, 307 Viral oncogenes, 557 v-erb, 614 Viral penetration and uncoating inhibitors, Vero cells, 359 128–129 Verruca plana, 696 Viral polymerases inhibitors, 117 Verruca vulgaris, 696 Viral proliferation and replication, 31–38 Vertical transmission, 150, 556 Viral proteases inhibitors, 119 Vesicles formation, 444 Viral proteins, 443–446, 481–493 Vesicular disease, 352 of arenaviruses, 443 Vesicular exanthema virus, 245 orthomyxoviruses, 481 Vesicular stomatitis virus, 352, 369 Viral transduction, 9 clinical features, 369 Virion-associated protein rapid. See Vpr diagnosis, 369 protein epidemiology and transmission, 369 Virion infectivity factor, 581 genome organization, 355 Virions, 26 pathogenesis, 369 Virocrine stimulation, 691 Vesiculovirus, 352 Viroids, 28–29 Vesivirus, 236 plant pathogenic, 651 genome organization, 239 Virokines, 841 v-fms, 615 Virology, future challenges, 14 Vhs protein, 763 Virophages, 28–29 Vif Protein, 581 Viroplasms, 539 vIL-6, 775, 787 Virosome, 53 Viraemia, 43 Virostatic drugs, 116, 128 primary, 43 Virulence, definition, 41 secondary, 43 Virus-associated RNAI, 726 Viral capsid antigen (VCA), 813 Virus-associated RNAII, 727 Viral capsids symmetry forms, 27 Viruses, 7, 31–39, 41–47, 437–514 Viral CC chemokine inhibitor, 841 adaptation to hosts, 152 Viral cultivation, 164 attachment, 31 Viral cyclin D2, 783, 786–787 attenuated, 137 Viral diseases, therapy by cytokines, 112–113 autocrine cell growth stimulation, Viral FLIP, 775, 783, 787 61–62 Viral gene expression strategies, 33 as biological weapons, 160 Viral IL-6, 783 as a cause of cancer, 11 Viral infection, 39, 40, 51–54 cell transformation, 11 chronic, 54 definition, 17–30 consequences for the affected cells, 51 direct detection, 164 detection, 163 discovery, 5 effects on the synthesis of cytokines, 112 with a double-stranded DNA indirect detection, 176 genome, 626 resistance by blood group antigens, 244 with double-stranded, segmented RNA state of equilibrium, 54 genomes, 521–551 time course of disease, 40 emergence of novel viruses, 155 transmission, 149 erythrocytes agglutination, 263 typical course, 39 evasion of the immune response, 91–93 Viral integrase, 594 evolution, 155 Viral IRF-1 (vIRF-1), 775 gene expression strategies, 33 Viral IRF-2 (vIRF-2), 775 genetic recombination, 158 Index 1015

historical overview, 3–5 VP29, 233 human pathogenic, 150 VP34, 234 inception of infection, 31 VP40, 420–422 of infectious pancreatic necrosis of Vpg protein, 194 salmonids, 527 Vpr protein, 581 intrauterine transmission, 6 Vpu protein, 582 latent, 26 Vpx protein, 582 mutations, 130–131, 155 V segments, 89 pathogenesis, 39 v-src, 614 penetration, 32 protein detection, 165 reassortants, 157 W recently emerged, 159 Wang, D., 657 recombinant, 141 Warthin–Finkeldey giant cells, 53 release, 38 Warts, 678, 699 replicationally active, 26 HPV-associated, 699–700 residence, 150 spontaneous regression, 702 resistance tests, 180 therapy, 703 resistant against virostatic drugs, 131 types, 695 retroviruses, 35 Wart viruses, 695–704 SARS, 160 Watson, J.D., 9 satellite, 28 Weller, T.H., 187, 798 with single-stranded, non-segmented, Western blot tests, 165 negative-sense RNA genomes, 351 Western blotting, 165, 176 with single-stranded RNA genomes and Western equine encephalitis virus, double-stranded DNA as an 158, 293, 307 intermediate product, 555 West Nile virus, 19, 255, 266, 283 with single-stranded, segmented, negative- on the American Continent, 285 sense RNA genomes, 437 epidemiology and transmission, 283 spreading in the organism, 41 NS1 protein, 263 structural features, 26–30 pathogenesis, 284 Virus families prophylaxis, 284 molecular characteristics and in the USA, 285 prototypes, 18 Whitewater Arroyo virus, 439, 453 taxonomic classification, 30 Wild mouse species, 448 Virus-host shutoff, 51, 202, 211 Wiley, D., 488 Virus-infected cells, recognition by Williams, E., 937 T lymphocytes, 81 Wilson, I., 488 Virus of atypical avian influenza. See Winocour, E., 11 Newcastle disease virus Wollensak, J., 13 Virusoids, 28–29 World Health Organization, 513 Virus particle, enveloped, 27 Wrapped virions, 831 Virus-specific T cells detection, 179 WU polyomaviruses, 658, 671–672 Virus uptake/uncoating inhibitors, 120 Wuthrich,€ K., 924 Visna, 619 v-myb, 614 v-myc, 614, 615 X Vogt, M., 8, 11 XCL1, 110 Vogt, P.K., 556 XCL2, 110 Voltage-dependent anion channel 1 (VDAC1), XendoU, 313 491 X-linked lymphoproliferative (XLP) VP24, 420, 421 syndrome, 809 VP26, 233 X4 viruses, 586, 601, 604, 605 1016 Index

Y therapy and prophylaxis, 272 Yaba monkey tumour virus, vaccine, 272 24, 832, 847 YY1, 692, 886 Yellow fever virus, 5, 12, 19, 255, 269–272 attenuated, 137 Z attenuation, 272 Zaire ebolavirus, 426 clinical features, 271 Zanamivir, 120, 129, 513 epidemics, 269 Zidovudine, 121 epidemiology and transmission, 270 Zinke, G.F., 361 genome organization, 262 Zinkernagel, R.M., 6, 448 immune response and diagnosis, 271 Zoonoses, 14, 149 live vaccine strain 17D, 272 Zoonotic potential of BSE, 928 pathogenesis, 271 Z protein, 439, 444–446 polyprotein, 258 of arenaviruses, 444