Nongenetic Reactivation and Is Caused by the Action of the Uncoating Protein

Poxviruses Dr. Ali Hashemi Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Introduction Structure and Composition Poxviruses are the largest and most complex of viruses infecting humans. Poxviruses are large enough to be seen as featureless particles by light microscopy. By electron microscopy, they appear to be brick-shaped or ellipsoid particles. An outer lipoprotein membrane,or envelope, encloses a core and two structures of unknown function called lateral bodies Cont…. The core contains the large viral genome of linear double- stranded DNA. The DNA contains inverted terminal repeats of variable length, and the strands are connected at the ends by terminal hairpin loops. The chemical composition of a poxvirus resembles that of a bacterium. Vaccinia virus is composed predominantly of protein (90%), lipid (5%), and DNA (3%). Classification Poxviruses are divided into two subfamilies based on whether they infect vertebrate or insect hosts. Most of the poxviruses that can cause disease in humans are contained in the genera Orthopoxvirus and Parapoxvirus; there are also several that are classified in the genera Yatapoxvirus and Molluscipoxvirus. Cont… Cont… The orthopoxviruses have a broad host range affecting several vertebrates. They include ectromelia (mousepox), camelpox, cowpox, monkeypox, vaccinia, and variola (smallpox) viruses. Some poxviruses have a restricted host range and infect only rabbits (fibroma and myxoma) or only birds. Others infect mainly sheep and goats (sheeppox, goatpox) or cattle (pseudocowpox, or milker’s nodule). Poxvirus replication Poxviruses are unique among DNA viruses in that the entire multiplication cycle takes place in the cytoplasm of infected cells. Poxviruses are further distinguished from all other animal viruses by the fact that the uncoating step requires a newly synthesized, virus-encoded protein. Cont… A. Virus Attachment, Penetration, and uncoating Virus particles establish contact with the cell surface and fuse with the cell membrane. Some particles may appear within vacuoles. Viral cores are released into the cytoplasm. Poxviruses inactivated by heat can be reactivated either by viable poxviruses or by poxviruses inactivated by nitrogen mustards (which inactivate the DNA). Cont… This process is called nongenetic reactivation and is caused by the action of the uncoating protein. Heat-inactivated virus alone cannot cause second-stage uncoating because of the heat lability of the RNA polymerase. Apparently, the heat-killed virus provides the template and the second virus provides the enzymes needed for transcription. Cont… B. replication of Viral DNA and Synthesis of Viral Proteins Among the early proteins made after vaccinia virus infection are enzymes involved in DNA replication, including a DNA polymerase and thymidine kinase. C. Maturation An antiviral drug affects the morphogenesis of poxvirus particles. Rifampin can block the formation and assembly of the vaccinia virus envelope. Cont… D. Virus-Encoded Host Modifier Genes Several poxvirus genes resemble mammalian genes for proteins that would inhibit host defense mechanisms. Examples include tumor necrosis factor receptor, interferon-γ receptor, interleukin-1 receptor, and a complement-binding protein. POXVIRUS INFECTIONS IN HUMANS: VACCINIA AND VARIOLA Edward Jenner introduced vaccination with live cowpox virus in 1798. Comparison of Vaccinia and Variola Viruses Vaccinia virus, the agent used for smallpox vaccination, is a distinct species of Orthopoxvirus. Vaccinia virus may be the product of genetic recombination, a new species derived from cowpox virus or variola virus by serial passage, or the descendant of a now extinct viral genus. Pathogenesis and Pathology of Smallpox The portal of entry of variola virus was the mucous membranes of the upper respiratory tract. In the preeruptive phase, the disease was barely infective. By the sixth to ninth day, lesions in the mouth tended to ulcerate and discharge virus. Thus, early in the disease, infectious virus originated in lesions in the mouth and upper respiratory tract. Later, pustules broke down and discharged virus into the environment of the smallpox patient. Clinical Findings The incubation period of variola (smallpox) was 10–14 days.The onset was usually sudden. One to 5 days of fever and malaise preceded the appearance of the exanthems, which began as macules, then papules, then vesicles, and finally pustules. These formed crusts that fell off after about 2 weeks, leaving pink scars that faded slowly. In each affected area, the lesions were generally found in the same stage of development (in contrast to chickenpox). Immunity Vaccination with vaccinia induced immunity against variola virus for at least 5 years and sometimes longer. Production of interferon is another possible immune mechanism. Laboratory Diagnosis The tests depend on identification of viral DNA or antigen from the lesion, direct microscopic examination of material from skin lesions, recovery of virus from the patient, and, least importantly, demonstration of antibody in the blood. Virus isolation can also be carried out by inoculation of vesicular fluid onto the chorioallantoic membrane of chick embryos. The parapoxviruses, molluscum contagiosum virus, and tanapoxvirus do not grow on the membrane. Treatment Vaccinia immune globulin is prepared from blood from persons vaccinated with the vaccinia virus. Methisazone : It is effective as prophylaxis but is not useful in treatment of established disease. Cidofovir Epidemiology Transmission of smallpox occurred by contact between cases.Smallpox was highly contagious. The virus was stable in the extracellular environment but was most commonly transmitted by respiratory spread. Patients were most highly infectious during the first week of rash after the fever had begun. Respiratory droplets were infectious earlier than skin lesions. Cont… There was no known nonhuman reservoir. There was one stable serotype. There was an effective vaccine. Vaccinia virus for vaccination is prepared from vesicular lesions (“lymph”) produced in the skin of calves, or it can be grown in chick embryos. The final vaccine contains 40% glycerol to stabilize the virus and 0.4% phenol to destroy bacteria. vector for introducing foreign genes for immunization purposes and as oncolytic viral therapy for cancer. Time of Vaccination Vaccinating between 1 and 2 years Primary take Revaccination Adverse reactions of Vaccination: Inadvertent autoinoculation-Contact transmission Eczema vaccinatum-Generalized vaccinia Progressive vaccinia-Fetal vaccinia Postvaccinial central nervous system disease MONKEYPOX INFECTIONS zoonosis It is probably acquired by direct contact with wild animals killed for food and skins. The primary reservoir host is not known, but squirrels and rodents can be infected. COWPOX INFECTIONS The natural reservoir of cowpox seems to be a rodent, and both cattle and humans are only accidental hosts. Domestic cats also are susceptible to cowpox virus. BUFFALOPOX INFECTIONS There is some concern that human-to-human transmission may also occur. ORF VIRUS INFECTIONS The virus of orf is a species of Parapoxvirus. It causes a disease in sheep and goats that is prevalent worldwide. Orf is transmitted to humans by direct contact with an infected animal. Infection of humans occurs usually as a single lesion on a finger, hand, or forearm but may appear on the face or neck. MOLLUSCUM CONTAGIOSUM Only in humans. The virus has not been transmitted to animals and has not been grown in tissue culture. The lesions of this disease are small, pink, wart-like tumors on the face, arms, back, and buttocks. TANAPOX AND YABA MONKEY TUMOR POXVIRUS INFECTIONS They do not grow on the chorioallantoic membrane of embryonated eggs. Rabies, Slow Virus Infections, and Prion Diseases Dr. Ali Hashemi Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran RABIES Rabies is an acute infection of the central nervous system that is almost always fatal. The virus is usually transmitted to humans from the bite of a rabid animal. Single-stranded RNA, linear, nonsegmented, negative-Sense. Virions contain an RNA-dependent RNA polymerase. Classification The viruses are classified in the family Rhabdoviridae . Rabies viruses belong to the genus Lyssavirus, whereas the vesicular stomatitis-like viruses are members of the genus Vesiculovirus. The Rhabdoviruses are very widely distributed in nature,infecting vertebrates, invertebrates, and plants. Rabies is the only medically important rhabdovirus. Many of the animal rhabdoviruses infect insects, but rabies virus does not. Reactions to Physical and Chemical Agents Rabies virus survives storage at 4°C for weeks and at –70°C for years. It is inactivated by CO2 , so on dry ice it must be stored in glass-sealed vials. Rabies virus is killed rapidly by exposure to ultraviolet radiation or sunlight, by heat (1 hour at 50°C), by lipid solvents (ether, 0.1% sodium deoxycholate),by trypsin, by detergents, and by extremes of pH. Virus replication Animal Susceptibility and Growth of Virus The virus is widely distributed in infected animals, especially in the nervous system, saliva, urine, lymph, milk, and blood. Recovery from infection is rare except in certain bats, where the virus has become peculiarly adapted to the salivary glands. There is a single serotype of rabies virus. Pathogenesis and Pathology

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