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Small DNA Viruses and Poxviruses

Small DNA Viruses and Poxviruses. Parvovirus Very small single-strand DNA viruses. Can only replicate in dividing cells. Some ​parvoviruses called “dependoviruses” require a helper virus (hence the adeno -associated viruses ).

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Small DNA Viruses and Poxviruses

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  1. Small DNA Viruses and Poxviruses

  2. Parvovirus • Very small single-strand DNA viruses. • Can only replicate in dividing cells. • Some ​parvoviruses called “dependoviruses” require a helper virus (hence the adeno-associated viruses)

  3. Because they require replication, they favor bone marrow, GI tract, and fetuses. • Adeno-associated virus doesn’t cause disease but integrates its DNA into chromosome 19 ​so it may be a good gene therapy vector.

  4. ​- icosahedra, ssDNA • ​- small genome (~5 kB) and inability to stim host DNA synthesis means reliance on host polymerases • ​- temperature and pH stable, but inactivated by chemical agents • ​- 2 ORFs: one for structural proteins, the other for nonstructural proteins

  5. PARVOVIRUSE B19 • ​- relies on globoside as receptor (blood group P antigen) • ​- cytopathic effect: giant pronormoblasts, nuclear inclusion, cytoplasmic vacuolization

  6. - infects nonpermissive cells (megaK), killing them without virus propagation • ​- Fetus: can cause severe anemia and hydrops fetalis • ​- Children: flu-like symptoms, flushed cheeks, extension of rash to extremities

  7. In normal children, B19 causes fever, myalgia, and a very red rash on the face. This ​constellation is called the “fifth disease.” • In normal adults, B19 causes arthritis and a minor anemia. • In adults with chronic anemias, B19 can be deadly.

  8. ​--Sickle cell anemia patients get transient aplastic anemia. • ​--Immunodeficient patients get chronic red cell aplasia • ​- Acute infection destroys erythroid precursors, important if pre-existing anemia • ​- Respiratory transmission, diagnose by PCR or ELISA, usually clears without treatment

  9. Papoviruses • The main virus to know from this family is HPV, which has a circular double-stranded ​DNA complexed with histones. • HPV replicates only in the nucleus of squamous epithelial cells (tissue tropism). • ​“Early genes” E2,E6, E7 encode regulatory proteins. • Cutaneous HPV enters through skin, infects basal layer, and causes warts.

  10. As the ​infected basal cells differentiate into Keratinocytes, late genes encoding capsid ​proteins are produced, and infectious virions are ready to go. • The incubation ​period can last years. • Thus, only differentiating cells produce infectious virions. • Mucosal HPV can transform squamous cells into carcinomas. • All cervical carcinoma is ​associated with HPV, especially HPV-16 and HPV-18.

  11. Oncogenicity is ​associated with the E6 and E7 proteins. E6 can complex with p53 and target it ​for ubiquity degradation. • E7 binds pRB (a tumor suppressor), which activates ​DNA synthesis and progression to S-phase. • In malignant cells, the viral genome integrates in a way that disrupts E2 control over E6 ​and E7. • This leaves these two transforming proteins intact and unregulated.

  12. Polyoma Viruses • Infection is very common, but disease uncommon except in Immunodeficient patients. • BK virus causes hemorrhagic cystitis. • JC virus causes a fatal demyelinating disease called progressive multifocal ​leukoencephalophathy (PML) seen in AIDS patients.

  13. Poxviruses • These are complex double-stranded DNA viruses. • They replicate in host cytoplasm, as ​opposed to nucleus. • This is a unique feature of poxviruses. Virions are enveloped, ​rectangular, and visible in the light microscope. • It carries its own transcription ​enzymes. Conserved genes at center of genome, and non-essential genes at the ends.

  14. Smallpox is transmitted by respiratory secretions, and replicates in macrophages. Lesions ​in the oropharynx and skin, including palms and soles. • Lesions go from papules ​to vesicles to pustules to scabs. Rash accompanied by vomiting, diarrhea, toxemia. • First “vaccine” was variolation (intranasal application of dried scabs).

  15. Then Edward ​Jenner in 1798 used cowpox. Now we use the vaccinia virus for smallpox vaccine. • Molluscum contagiosum causes small firm papules on exposed skin. It is no big deal. • Monkey pox was spread to American prairie dogs from African rodents. It may increase its ​adaptation to humans and cause widespread disease.

  16. Polyomaviruses • ​- Only important in immunosuppression • ​- BK causes hemorrhagic cystitis • ​- JC causes progressive multifocal leukoencephalopathy (esp. in AIDS) • ADENOASSOCIATED VIRUS (AAV) • ​- does not cause dz, but used as a gene therapy vector

  17. Papillomaviruses • ​​- Early genes (E1-7) and late genes (L1-2) • ​- E2: regulates switch from early to late gene expression, particularly downregulates E6 and E7, disruption of E2 implicated in cervical cancer

  18. ​​- E6: activates telomerase, in high-risk HPV complexes with p53 via E6AP • ​​- E7: binds pRB thereby releasing E2F-1 and initiating DNA synthesis/cell cycle • ​​- Species-specific and tissue-specific types

  19. ​​​- Cutaneously, causes hyperplasia of basal cell and wart formation • ​​​- Mucosal: genital/oral/respiratory mucosa • ​​​- Genital: e.g. cervix (condyloma) • ​- HPV can cause cervical intraepithelial neoplasia screen by Pap smear

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