Drift, Shift, and Attenuation
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Technical Glossary
WBVGL 6/28/03 12:00 AM Page 409 Technical Glossary abortive infection: Infection of a cell where there is no net increase in the production of infectious virus. abortive transformation: See transitory (transient or abortive) transformation. acid blob activator: A regulatory protein that acts in trans to alter gene expression and whose activity depends on a region of an amino acid sequence containing acidic or phosphorylated residues. acquired immune deficiency syndrome (AIDS): A disease characterized by loss of cell-mediated and humoral immunity as the result of infection with human immunodeficiency virus (HIV). acute infection: An infection marked by a sudden onset of detectable symptoms usually followed by complete or apparent recovery. adaptive immunity (acquired immunity): See immunity. adjuvant: Something added to a drug to increase the effectiveness of that drug. With respect to the immune system, an adjuvant increases the response of the system to a particular antigen. agnogene: A region of a genome that contains an open reading frame of unknown function; origi- nally used to describe a 67- to 71-amino acid product from the late region of SV40. AIDS: See acquired immune deficiency syndrome. aliquot: One of a number of replicate samples of known size. a-TIF: The alpha trans-inducing factor protein of HSV; a structural (virion) protein that functions as an acid blob transcriptional activator. Its specificity requires interaction with certain host cel- lular proteins (such as Oct1) that bind to immediate-early promoter enhancers. ambisense genome: An RNA genome that contains sequence information in both the positive and negative senses. The S genomic segment of the Arenaviridae and of certain genera of the Bunyaviridae have this characteristic. -
Current and Novel Approaches in Influenza Management
Review Current and Novel Approaches in Influenza Management Erasmus Kotey 1,2,3 , Deimante Lukosaityte 4,5, Osbourne Quaye 1,2 , William Ampofo 3 , Gordon Awandare 1,2 and Munir Iqbal 4,* 1 West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Accra P.O. Box LG 54, Ghana; [email protected] (E.K.); [email protected] (O.Q.); [email protected] (G.A.) 2 Department of Biochemistry, Cell & Molecular Biology, University of Ghana, Legon, Accra P.O. Box LG 54, Ghana 3 Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra P.O. Box LG 581, Ghana; [email protected] 4 The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK; [email protected] 5 The University of Edinburgh, Edinburgh, Scotland EH25 9RG, UK * Correspondence: [email protected] Received: 20 May 2019; Accepted: 17 June 2019; Published: 18 June 2019 Abstract: Influenza is a disease that poses a significant health burden worldwide. Vaccination is the best way to prevent influenza virus infections. However, conventional vaccines are only effective for a short period of time due to the propensity of influenza viruses to undergo antigenic drift and antigenic shift. The efficacy of these vaccines is uncertain from year-to-year due to potential mismatch between the circulating viruses and vaccine strains, and mutations arising due to egg adaptation. Subsequently, the inability to store these vaccines long-term and vaccine shortages are challenges that need to be overcome. Conventional vaccines also have variable efficacies for certain populations, including the young, old, and immunocompromised. -
Adenoviral Vector-Based Vaccine Platforms for Developing the Next Generation of Influenza Vaccines
Review Adenoviral Vector-Based Vaccine Platforms for Developing the Next Generation of Influenza Vaccines Ekramy E. Sayedahmed 1 , Ahmed Elkashif 1, Marwa Alhashimi 1, Suryaprakash Sambhara 2,* and Suresh K. Mittal 1,* 1 Department of Comparative Pathobiology, Purdue Institute for Immunology, Inflammation and Infectious Disease, Purdue University Center for Cancer Research, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA; [email protected] (E.E.S.); [email protected] (A.E.); [email protected] (M.A.) 2 Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA * Correspondence: [email protected] (S.S.); [email protected] (S.K.M.) Received: 2 August 2020; Accepted: 17 September 2020; Published: 1 October 2020 Abstract: Ever since the discovery of vaccines, many deadly diseases have been contained worldwide, ultimately culminating in the eradication of smallpox and polio, which represented significant medical achievements in human health. However, this does not account for the threat influenza poses on public health. The currently licensed seasonal influenza vaccines primarily confer excellent strain-specific protection. In addition to the seasonal influenza viruses, the emergence and spread of avian influenza pandemic viruses such as H5N1, H7N9, H7N7, and H9N2 to humans have highlighted the urgent need to adopt a new global preparedness for an influenza pandemic. It is vital to explore new strategies for the development of effective vaccines for pandemic and seasonal influenza viruses. The new vaccine approaches should provide durable and broad protection with the capability of large-scale vaccine production within a short time. The adenoviral (Ad) vector-based vaccine platform offers a robust egg-independent production system for manufacturing large numbers of influenza vaccines inexpensively in a short timeframe. -
Detection of Influenza a Viruses from Environmental Lake and Pond Ice
TITLE “DETECTION OF INFLUENZA A VIRUSES FROM ENVIRONMENTAL LAKE AND POND ICE” Zeynep A. Koçer A Dissertation Submitted to the Graduate College of Bowling Green State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY August 2010 Committee: Scott O. Rogers, Advisor W. Robert Midden Graduate Faculty Representative John Castello George Bullerjahn Paul Morris ii ABSTRACT Scott O. Rogers, Advisor Environmental ice is an ideal matrix for the long-term protection of organisms due to the limitation of degradative processes. As a result of global climate change, some glaciers and polar ice fields are melting at rapid rates. This process releases viable microorganisms that have been embedded in the ice, sometimes for millions of years. We propose that viral pathogens have adapted to being entrapped in ice, such that they are capable of infecting naïve hosts after melting from the ice. Temporal gene flow, which has been termed genome recycling (Rogers et al., 2004), may allow pathogens to infect large host populations rapidly. Accordingly, we hypothesize that viable influenza A virions are preserved in lake and pond ice. Our main objective was to identify influenza A (H1-H16) from the ice of a few lakes and ponds in Ohio that have high numbers of migratory and local waterfowl visiting the sites. We developed a set of hemagglutinin subtype-specific primers for use in four multiplex RT-PCR reactions. Model studies were developed by seeding environmental lake water samples in vitro with influenza A viruses and subjecting the seeded water to five freeze-thaw cycles at -20oC and -80oC. -
Evolution and Adaptation of the Avian H7N9 Virus Into the Human Host
microorganisms Review Evolution and Adaptation of the Avian H7N9 Virus into the Human Host Andrew T. Bisset 1,* and Gerard F. Hoyne 1,2,3,4 1 School of Health Sciences, University of Notre Dame Australia, Fremantle WA 6160, Australia; [email protected] 2 Institute for Health Research, University of Notre Dame Australia, Fremantle WA 6160, Australia 3 Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, The University of Western Australia, Nedlands WA 6009, Australia 4 School of Medical and Health Sciences, Edith Cowan University, Joondalup WA 6027, Australia * Correspondence: [email protected] Received: 19 April 2020; Accepted: 19 May 2020; Published: 21 May 2020 Abstract: Influenza viruses arise from animal reservoirs, and have the potential to cause pandemics. In 2013, low pathogenic novel avian influenza A(H7N9) viruses emerged in China, resulting from the reassortment of avian-origin viruses. Following evolutionary changes, highly pathogenic strains of avian influenza A(H7N9) viruses emerged in late 2016. Changes in pathogenicity and virulence of H7N9 viruses have been linked to potential mutations in the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA), as well as the viral polymerase basic protein 2 (PB2). Recognizing that effective viral transmission of the influenza A virus (IAV) between humans requires efficient attachment to the upper respiratory tract and replication through the viral polymerase complex, experimental evidence demonstrates the potential H7N9 has for increased binding affinity and replication, following specific amino acid substitutions in HA and PB2. Additionally, the deletion of extended amino acid sequences in the NA stalk length was shown to produce a significant increase in pathogenicity in mice. -
Perspectives
PERSPECTIVES in humans. In the 1957 H2N2-SUBTYPE pan- OPINION demic virus, both influenza surface proteins, HA and neuraminidase (NA), and one inter- nal protein, polymerase B1 (PB1), were Evidence of an absence: closely related to Eurasian wild waterfowl influenza proteins6,7.In 1968, the H3N2 pan- the genetic origins of the 1918 demic virus contained novel HA and PB1 proteins, also apparently of Eurasian wild waterfowl origin7,8.Although it is not known pandemic influenza virus exactly how these reassortant viruses were generated, pigs can be infected with both Ann H. Reid, Jeffery K. Taubenberger and Thomas G. Fanning avian and human influenza strains and this species has been suggested as a potential ‘mix- Abstract | Annual outbreaks of influenza A (HA) protein on the virus surface can greatly ing vessel’ for the generation of pandemic infection are an ongoing public health threat reduce the effectiveness of existing antibodies, viruses2,9. and novel influenza strains can periodically leaving people vulnerable to repeated influenza In 1918, the most devastating influenza emerge to which humans have little immunity, infections throughout their lives. In addition pandemic in history killed at least 40 million resulting in devastating pandemics. The 1918 to this gradual change in the influenza virus, people10,11.In addition to a death toll that is pandemic killed at least 40 million people which is known as ANTIGENIC DRIFT, influenza A several times higher than that of other worldwide and pandemics in 1957 and 1968 viruses can acquire novel surface proteins influenza pandemics, the 1918 H1N1 virus caused hundreds of thousands of deaths. -
Cdc Pandemic Influenza Questions and Answers 10-20-2017
CDC PANDEMIC INFLUENZA QUESTIONS AND ANSWERS • What is an influenza pandemic? o An influenza pandemic is a global outbreak of a new influenza A virus that is very different from current and recently circulating human seasonal influenza A viruses. Pandemics happen when new (novel) influenza A viruses emerge which are able to infect people easily and spread from person to person in an efficient and sustained way. • Where do pandemic influenza viruses come from? o Different animals—including birds and pigs—are hosts to influenza A viruses that do not normally infect people. Influenza A viruses are constantly changing, making it possible on very rare occasions for non-human influenza viruses to change in such a way that they can infect people easily and spread efficiently from person to person • How do influenza A viruses change to cause a pandemic? o Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: the hemagglutinin (H) and the neuraminidase (N). There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes (H1 through H18 and N1 through N11). Theoretically, any combination of the 18 hemagglutinins and 11 neuraminidase proteins are possible, but not all have been found in animals and even fewer have been found to infect humans. o Influenza viruses can change in two different ways one of which is called “antigenic shift” and can result in the emergence of a new influenza virus. Antigenic shift represents an abrupt, major change in an influenza A virus. This can result from direct infection of humans with a non- human influenza A virus, such as a virus circulating among birds or pigs. -
Highly Pathogenic Avian Influenza
Importance Avian Influenza Avian influenza viruses are highly contagious, extremely variable viruses that are widespread in birds. Wild birds in aquatic habitats are thought to be their natural Fowl Plague, Grippe Aviaire reservoir hosts, but domesticated poultry are readily infected. Most viruses cause only mild disease in poultry, and are called low pathogenic avian influenza (LPAI) viruses. Highly pathogenic avian influenza (HPAI) viruses can develop from certain LPAI Last Updated: September 2014 viruses, usually while they are circulating in poultry flocks. HPAI viruses can kill up to 90-100% of the flock, and cause epidemics that may spread rapidly, devastate the poultry industry and result in severe trade restrictions. Infection of poultry with LPAI viruses capable of evolving into HPAI viruses also affects international trade. Avian influenza viruses occasionally affect mammals, including humans, usually after close contact with infected poultry. While many human cases are limited to conjunctivitis An enhanced version of or mild respiratory disease, some viruses tend to cause severe illness. In rare cases, this factsheet, with citations avian influenza viruses can become adapted to circulate in a mammalian species, and is available at these viruses have caused or contributed to at least three pandemics in humans. http://www.cfsph.iastate.edu/ Factsheets/pdfs/highly_patho Etiology genic_avian_influenza- Avian influenza results from infection by viruses belonging to the species citations.pdf influenza A virus, genus influenzavirus A and family Orthomyxoviridae. Influenza A viruses are classified into subtypes based on two surface proteins, the hemagglutinin (HA) and neuraminidase (NA). At least 16 hemagglutinins (H1 to H16), and 9 neuraminidases (N1 to N9) have been found in viruses from birds, while two additional HA and NA types have been identified, to date, only in bats. -
V Iral Evolution
4 Viral evolution Molecular evidence for evolution 4: Viral evolution | sr0299 teachers guide Molecular evidence for evolution 4: Viral evolution photo by AJ Cann Components NAME DESCRIPTION AUDIENCE Viral evolution This guide explains how to use bioinformatics tools teachers within the Influenza Research Database to build students’ teachers guide understanding of molecular evidence for evolution. Influenza This background sheet for teachers describes the structure teachers and reproduction of influenza viruses. background sheet Investigating influenza This background sheet for teachers describes how influenza teachers viruses evolve and mechanisms of antigenic drift and background sheet shift. It provides an introduction to bioinformatics and the Influenza Research Database. Fighting the ‘flu This factsheet describes the structure of influenza viruses students and how they evolve through antigenic shift and drift. fact sheet Influenza – an evolving This activity sheet guides students through interactive use students problem! of the Influenza Research Database. worksheet Purpose Outcomes Students develop an understanding of how databases Students understand that: may be used to map changes in influenza viruses as • there are different types of influenza virus that they evolve. affect different animal species; • evolution can occur rapidly in viruses, through mechanisms of antigenic drift and antigenic shift; • mutations or changes in nucleotide sequences of viruses mean hosts may not recognise a virus; and • online databases, such as the Influenza Research Database, enable scientists to track strains of viruses and map evolutionary changes, as they occur. Activity summary ACTIVITY POSSIBLE STRATEGY Students read the fact sheet, Fighting the ‘flu, to provide background individually or in pairs information for an online database activity. -
Replication Strategies of RNA Viruses Requiring RNA-Directed Mrna 16 Transcription As CHAPTER the First Step in Viral Gene Expression
WBV16 6/27/03 11:21 PM Page 257 Replication Strategies of RNA Viruses Requiring RNA-directed mRNA 16 Transcription as CHAPTER the First Step in Viral Gene Expression ✷ REPLICATION OF NEGATIVE-SENSE RNA VIRUSES WITH A MONOPARTITE GENOME ✷ The replication of vesicular stomatitis virus — a model for Mononegavirales ✷ Paramyxoviruses ✷ Filoviruses and their pathogenesis ✷ Bornaviruses ✷ INFLUENZA VIRUSES — NEGATIVE-SENSE RNA VIRUSES WITH A MULTIPARTITE GENOME ✷ Involvement of the nucleus in flu virus replication ✷ Generation of new flu nucleocapsids and maturation of the virus ✷ Influenza A epidemics ✷ OTHER NEGATIVE-SENSE RNA VIRUSES WITH MULTIPARTITE GENOMES ✷ Bunyaviruses ✷ Arenaviruses ✷ VIRUSES WITH DOUBLE-STRANDED RNA GENOMES ✷ Reovirus structure ✷ The reovirus replication cycle ✷ Pathogenesis ✷ SUBVIRAL PATHOGENS ✷ Hepatitis delta virus ✷ Viroids ✷ Prions ✷ QUESTIONS FOR CHAPTER 16 WBV16 6/27/03 3:58 PM Page 258 258 BASIC VIROLOGY A significant number of single-stranded RNA viruses contain a genome that has a sense opposite to mRNA (i.e., the viral genome is negative-sense RNA). To date, no such viruses have been found to infect bacteria and only one type infects plants. But many of the most important and most feared human pathogens, including the causative agents for flu, mumps, rabies, and a number of hemorrhagic fevers, are negative-sense RNA viruses. The negative-sense RNA viruses generally can be classified according to the number of segments that their genomes contain. Viruses with monopartite genomes contain a single piece of virion negative-sense RNA, a situation equivalent to that described for the positive-sense RNA viruses in the last chapter. A number of groups of negative-sense RNA viruses have multipartite (i.e., seg- mented ) genomes. -
Influenza: a Seasonal Disease
Influenza: A seasonal disease FACTFILE Influenza: A seasonal disease nfluenza or ‘flu’ is a common viral addition, global influenza pandemics proteins that the virus needs in order disease of the upper respiratory tract have been recorded throughout history to replicate inside the infected host cell. Iin humans (in birds it is an infection and they seem to occur every 10 to 40 The genome is protected by a membrane of the gut). There are three types of years. Between 1918 and 1919 flu is envelope. Protruding from the virus influenza virus: influenza A, B and C. thought to have killed over 50 million membrane are hundreds of copies of two However, a fourth type, influenza D, people (6 times as many as died as a different varieties of viral glycoprotein has recently been discovered as a consequence of the first-world war). It spikes. Approximately 80% of the veterinary infection, particularly of was caused by an unusually pathogenic spikes are haemagglutinin (HA) and the cows. Major outbreaks of influenza are strain of influenza A virus. remaining 20% are neuraminidase (NA). associated with influenza virus type A The HA and NA surface proteins are or B. Influenza C is common but seldom What causes flu? involved in viral attachment and entry causes disease The influenza virus particle – virion to host cells as well as the release of Influenza A is commonly associated – is usually spherical, but sometimes new virions. They are also the main part with human disease. Each year, many filamentous, in shape and carries its of the virus recognised by our immune countries, including the UK, experience genetic material on eight pieces of single system as foreign, and most of the seasonal influenza epidemics that affect stranded RNA known as segments. -
Fected with Certain Pox Viruses (E.G
A A-type inclusion body. Inclusion bodies pro abortive transformation. A TRANSFORMATION of duced late in infection in the cytoplasm of cells in cells which is unstable so the cells revert to fected with certain pox viruses (e.g. fowlpox, normal after a few generations. ectromelia, cowpox, canarypox). Some contain virus particles. In cowpox virus infections the abras virus. Family Bunyaviridae, genus inclusions consist almost entirely of a single pro Bunyavirus. tein species (mw. 160 x 103), abundantly synthe sised late in infection. Cytoplasmic A-type inclu Abraxas grossulariata Cytoplasmic Polyhe sions of some vertebrate poxviruses (e.g. drosis Virus. CYTOPLASMIC POL YHEADROSIS VIRUS fowlpox) resemble POLYHEDRA in several proper ( CPV) isolated in the United Kingdom from larvae ties as they contain virus particles, are infective, of the magpie moth, Abraxas grossutariata can be isolated intact, are resistant to digestion by (Geometridae, Lepidoptera). The virus is the type some proteases and are extremely resistant to member of 'type 8' CPVs. Unrelated to Bombyx prolonged storage. mori (type I) CPV on the basis of RNA electro Patel, D.O. et at. ( 1986) Virology 149, 174. pherotype. Viruses of similar electropherotype have been observed in other Lepidoptera (see A-type virus particle. A term used originally for APPENDIX B). a morphologically defined group of RNA virus Payne, C.C. and Mertens, P.P.C. (1983) In The particles, often found in tumour cells. They are Reoviridae. p. 425. ed. W.K. Joklik. Plenum double-shelled spherical particles with a diameter Press: New York. of 65-75 nm. for the outer and 50 nm.