POXVIRIDAE

Introduction Poxviruses are the largest and most complex of viruses that infect vertebrates. They are large enough to be seen under the light microscope. Smallpox, the great success story in the fight against infectious disease This provides at least three ‘firsts’: the first vaccine, the first disease to be totally eradicated by immunization, and the first virus infection against which chemotherapy was clinically effective.

Introduction Poxviridae contains two subfamilies: The Chordopoxvirinae, the poxviruses of vertebrates, and Entomopoxvirinae, the poxviruses of insects. Chordopoxvirinae are placed in eight genera, the following table enumerate those that can infect human Viruses are distinguished on the basis of morphology, genome structure, growth characteristics and serological reactions There is cross-reaction between genera

Poxviruses that infect humans Genus Virus Primary host(s) Clinical features in humans Orthopoxvirus Variola Man Smallpox Vaccinia Vesicular vaccination lession Cowpox Cattle, cats, rodents Lesions on hands Monkeypox Monkey, squirrels Resembles smallpox Parapoxvirus Pseudocowpox Cattle Localized nodular lesions (milkers’ nodes) Yatapoxvirus Orf Sheep, goats Localized vesiculo. Granulomatous lesions Tanpox Monkeys Vesicular skin lesions and febrile illness Yabapox Human infections very rare and accidental; localized skin tumors Molluscipoxvirus Molluscum contagiosum Multiple small skin nodules A granuloma is a focal area of chronic inflammation produced by circulating monocytes as part of an immunologic process. A granulomatous reaction is characterized histologically by transformed macrophages (epithelioid cells) surrounded by lymphocytes. 

General Characteristics The largest viruses of all They measure 230x270 nm Orthopoxviruses are brick-shaped, Orf and molluscum contagiosum are ovoid When stained, can be seen with ordinary microscope DNA is double-stranded Molecular weight of the genome is about 108 The genome codes for more than 100 polypeptides, including DNA-dependent RNA polymerase and other enzymes, there is a common internal family antigen in the core

General Characteristics Propagation on chorioallantoic membrane of chick embryos producing lesions (pocks) and in tissue culture. Unlike most DNA viruses, the poxviruses replicate only in the cytoplasm, in which they form inclusion bodies; eosinophilic cytoplasmic inclusions (Guarnieri bodies). Preference for epidermal cells. Vaccine is prepared by infecting calves with vaccinia virus, scrapings of lesions are used as intradermal. In 1977, World Health Organization (WHO) announced that smallpox was eradicated worldwide. Immunity develops 8-10 days after vaccination

Epidemiology Transmission At risk or risk factors Distribution Smallpox: respiratory droplets, contact with virus on fomites Other poxviruses: direct contact or fomites At risk or risk factors Molluscum contagiosum: sexual contact Pet owners, animal handlers (contact with lesion) Distribution Worldwide No seasonal incidence Vaccines or antiviral drugs Attenuated vaccine against smallpox (vaccinia virus) objects or materials that are likely to carry infection, such as clothes, utensils, and furniture.

Epidemiology Smallpox and molluscum contagiousum are strictly human viruses. In contrast, the natural hosts for the other poxviruses important to humans are vertebrates other than humans (e.g., cow, sheep, goats). The viruses infect humans only through accidental or occupational exposure (zoonosis).

Pathogenesis After being inhaled, smallpox virus replicates in the upper respiratory tract. Dissemination occurs via lymphatic and cell-associated viremic spread. Internal and dermal tissues are inoculated after a second viremia, causing the simultaneous eruption of the characteristic pocks. Molluscum contagiosum and the other poxviruses, however, are acquired through direct contact with lesions.

Replication It takes place in cytoplasm Phagocytosis Transcription of early mRNA by the action of viral RNA polymerases: Enzymes degrading viral core Uncoating DNA replication Late transcription: Structural proteins Assembly of viral DNA into inner viral membrane Enclosure of viral core and lateral bodies by outer membrane Release from host cell

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Variola and Vaccinia Viruses Variola viruses: The variola virus is the causative agent of smallpox Variola has a narrow host range Smallpox used to occur in two distinct clinical varieties: Variola major or classical smallpox: The  complicated, highly fatal disease typically seen in Asia. Variola minor or alastrim: The mild, nonfatal disease (alastrim) typically seen in Latin America. Variola has a narrow host range (only humans and monkeys)

Variola and Vaccinia Viruses Vaccinia virus, the agent used for smallpox vaccination, is a distinct species of Orthopoxvirus. Vaccinia has a broad host range that includes rabbits and mice. At some time after Jenner’s original use of “cowpox” virus, the vaccine virus became “vaccinia virus”. Vaccinia virus is unique in that it is an ‘artificial virus’ and does not occur in nature as such. It may be the product of genetic recombination, a new species derived from cowpox virus or variola virus by serial passage.

Diagnosis Clinical picture Detection of viral antigen from skin scrapings Tissue culture, or on chorioallantoic membrane of chick embryo “pocks and Guarnieri bodies” Detection of specific antibodies Hemagglutinin inhibition

Control Vaccination-intradermal Chemotherapy Istatin-β-thiosemicarbazone (IBT): Inhibits translation of late mRNA Methisazone: inhibits morphogenesis Rifampin: Cidofovir: inhibits viral DNA polymerase

Cowpox and Monkeypox Cowpox Cowpox is, a zoonosis. Cowpox lesions are seen on the udder and teats of cows and may be transmitted to humans during milking. The lesions in humans usually appear on the hands or fingers. The natural reservoir of cowpox seems to be a rodent.

Cowpox and Monkeypox Monkeypox This orthopoxvirus zoonosis causes an illness in humans very similar to smallpox. Squirrels seem to be the main reservoir of infection, and the infection is seen mainly in children who may acquire it from playing with captive animals

Orf Orf (contagious pustular dermatitis or sore Mouth) Orf is a disease of sheep and goats transmitted to human beings by contact. It is an occupational disease of sheep handlers. In humans, the disease occurs as a single papulovesicular lesion with a central ulcer usually on the hand, forearm, or face.

Tanapox This virus takes its name from the Tana River in Kenya, where it was first diagnosed. It is prevalent in monkeys and appears to be spread by insect bites. Monkeys are the only animals susceptible. There is usually only one vesicular lesion but its appearance is preceded by fever and quite severe malaise. Recovery is uneventful.

Molluscum Contagiosum The result of the infection is usually a benign, mild skin disease characterized by lesions (growths) that may appear anywhere on the body. Within 6-12 months, Molluscum contagiosum typically resolves without scarring but may take as long as 4 years.