Medical Microbiology & Immunology Lecture 22 Virology Poxviruses 1) To know the poxviruses genera that infect humans. Orthopoxviruses Parapoxviruses Unclassified Variola major: smallpox 3-40% fatality Variola minor: (Alastrim) smallpox 1% fatality Cowpox: mild lesions on hands Vaccinia: used for vaccination Monkeypox: similar to smallpox (less severe) Orf: infection in sheep and goats. Human contact = single lesion, spontaneous regression Pseudocowpox: Milker's nodules (similar to orf) Molluscum contagiosum: contact (also sexual) "Pearl like" skin lesions, spontaneous regression 2) To describe the viral structure and replication. Structure: the most complex animal virus and largest (200-300 nm). Brick or oval shaped, dsDNA genome surrounded by 2 lateral bodies and enclosed in a membrane. Replication: rapidly adheres to receptors and is endocytized (cytoplasmic vacuole), first uncoating removes outer membrane, second uncoating partially removes core membranes and proteins, viral DNA-dependent RNA polymerase is activated, transcripts are translated into virus-coated enzymes which further degrade core proteins and release naked viral DNA. Early transcription leads to synthesis of viral DNA polymerase, late functions begin with DNA replication, host protein synthesis is inhibited by viral protein, assembled in the cytoplasm, and acquires an envelope membrane (probably from the Golgi complex). 3) To explain the clinical features of smallpox. Virus is inhaled and replicates in the upper respiratory tract epithelial cells before spreading to regional lymph nodes. Viremia: target cells or skin, mucous membranes and internal organs. Fever and malaise precede lesions, which are vesicles that appear on the face, arms, and lower extremities simultaneously. Outcome varies from mild to severe fulminant (genetics?). Convocations include: keratitis, encephalitis, pneumonia, and bacterial superinfections. 4) To recognize the pros and cons of smallpox vaccination. Vaccination is vaccinia virus given intradermally after one year of age. Pros: guards against infection and prevents the spread of the virus. Smallpox eradicated by who vaccination program, which began in 1967. Last known case occurred in 1977 in Somalia. Cons: protection is not lifelong, revaccination at 10-year intervals. Adverse reactions to the vaccine include: generalized vaccinia (vesicles over entire body), encephalitis (40% fatality), progressive vaccinia (immunosuppressed patients, lesions enlarge) 50% mortality, and death of fetus in pregnancy. 5) To describe the diagnosis and treatment of smallpox. Diagnosis: clinical picture, serology. Treatment: Methisazone (Marboran), reduces severity, must begin in early after infection. 6) To identify other diseases associated with poxviruses. See question 1. 7) To discuss its potential use as germ warfare or in bioterrorism. Because smallpox is one of the most stable enveloped viruses, it can be preserved for a long-time, if freeze dried. It is unaffected with environmental conditions, in fact the scab form is stable for one year at room temperature in as much as 13 years in a lab. It is in activated at 65°C for 30 minutes and with bleach, ethanol (70%). Using modern genetic recombination techniques, it may also be engineered to be more virulent.