1. 6/01: Papillomaviruses, polyomaviruses, and adenoviruses (Small DNA viruses) 6/10: Herpesviruses (Large DNA viruses) 6/15: Retroviruses (RNA in virions, integrated viral DNA in chromosomes)

2. 40~50 nm 70~90 nm 100~200 nm

3. 5~40 kb >100 kb

4. Viruses with oncogenic potential: Papillomaviruses Polyomaviruses Adenoviruses Herpesviruses Retroviruses Hepadnaviruses Flaviviruses HPV HCV HBV EBV, KSHV HTLV

5. Viral genome replication in nucleus!

6. I. Viral particle II. Viral genome III. Life cycle IV. Infection and immunity V. Diseases VI. Diagnosis VII. Treatment and control

7. Papillomaviruses

8. I.Viral particle: nonenveloped icosahedral capsid (resistant to inactivation!)

9. II. Viral genome: circular dsDNA (At least 100 types based on DNA sequence homology: very tissue-specific) (bp) E: early genes; L: late genes

10. III. Life cycle: Tissue/cell-dependent! E6, E7 E1, E2 L1, L2

11. Tumor suppressors

12. IV. Infection and immunity: Transmission: direct contact, sexual contact, birth canal Targets: skin (cutaneous HPV) or mucosa (mucosal HPV) Major pathogenesis: warts and tumors Local infection Immune control: innate and cell-mediated immunity Persistent infection and recurrence Symptomatic and asymptomatic infection and shedding

13. E6, E7 E1, E2 L1, L2 Low-level Ag expression Immuno-privileged site “Persistent infection”

14. V.Diseases: Skin warts: HPV 1~4 (3~4 months for development) Anogenital warts (condylomata acuminata): HPV 6, 11 Benign tumors (oral or laryngeal papillomas): HPV 6, 11 Cervical dysplasia and carcinoma: HPV 16, 18 (1~4 years for development) Anogenital or oropharyngeal cancers: HPV 16, 18

15. Warts:

16. Progression of HPV-mediated cervical carcinoma:

17. HPV DNA integration/breaking site in cervical carcinoma

18. VI. Diagnosis: Histological examination of warts (prickle cell hyperplasia and hyperkeratosis) Papanicolaou-stained cervical smear (Pap smear) (Koilocytotic cells) Detection of HPV DNA (PCR, in situ hybridization, sequencing/typing) Immunodetection of viral antigens No virus culture!

19. Koilocytosis (vacuolated cytoplasm) in Pap staining of HPV-infected cells

20. VII. Treatment and control: Removal of warts Induction of local inflammation (imiquimod, interferon) Local treatment with cidofovir (selective killing of HPV-infected) HPV vaccine (L1 viruslike particles of HPV 6, 11, 16, 18) (reduction of anogenital warts and cervical cancer) Safe sex and avoiding direct contact of infected tissues

21. Polyomaviruses BK virus and JC virus in human Simian vacuolating virus 40 (SV40) in monkey

22. I. Viral particle: nonenveloped capsid II. Viral genome: circular dsDNA 5 kb Early genes: For viral DNA replication Late genes: For virion assembly SV40 Large T antigen

23. Tumor suppressors

24. III. Life cycle:

25. IV. Infection: Transmission: maybe respiratory route Infection of lymphocytes and spread through viremia Ubiquitous, asymptomatic and persistent infection (infection before 15 yo) Latency: BK in kidney; JC in kidney, B cells or myeloid cells Reactivation during pregnancy (no effect on fetus) or in immunocompromised patients

26. V.Diseases: in immunocompromised patients BK virus: renal diseases Ureteral stenosis or hemorrhagic cystitis JC virus: progressive multifocal leukoencephalopathy (PML) Partial transformation of astrocytes (glioblastoma-like) Lysis of oligodendrocytes (demyelination) 10% of AIDS patients, dying within 2 years No human cancer

27. Immunocompromised

28. VI. Diagnosis: PML: brain lesions with demyelination in white matter PCR detection of viral DNA in urine or cerebrospinal fluid Immunodetection of viral antigens in affected tissues Urine cytologic test: enlarged cells with basophilic inclusions No virus isolation VII. Treatment and control? Prevention from immunosuppression

29. Adenoviruses

30. I.Viral particle: nonenveloped icosadeltahedral capsid (resistant to drying, detergents, protease, acid, mild chlorine) Viral attachment to cell receptors (Receptor: CAR) Virus entry through endocytosis (Coreceptor: integrin α v β 3 /α v β 5 ) Serotype-specific antigens Inhibition of host mRNA transport and protein synthesis Penton bases with fibers:

31. II. Viral genome: linear dsDNA with 5’ terminal protein

32. Tumor suppressors

34. E3 19 kD protein reduces MHC class I to prevent antigen presentation. E3 14.7 kD protein inhibits TNF-  production. /PKR

35. III. Life cycle: In permissive cells: Viral replication, cell death with virion production In nonpermissive cells: Latency with viral genomes in the nuclues Cell transformation in rodent cells

36. IV. Infection and immunity: Transmission: aerosol, close contact, fecal-oral routes Primary targets: mucoepithelial cells (serotype-dependent) Major pathogenesis: cell lysis and tissue damage Local infection and spread through viremia Immune control: antibody and cell-mediated immunity Persistent infection in lymphoid tissues Symptomatic and asymptomatic infection and shedding

37. Oral route

38. V.Diseases: Children (<14 yo) and people in crowded areas are at risk. Immunocompromised patients may have more serious diseases No human cancer (Ad 4, 7) (Ad 1, 2, 5, 6) (Ad 40-42)

39. Adenovirus respiratory infection

40. VI. Diagnosis: Virus isolation from affected tissues (culture in epithelial cells, ~ 6 days) Detection, typing, and grouping by immunoassay or PCR VII. Treatment and control: No approved treatment for adenovirus infection Live Ad 4 and 7 vaccines for military recruits Careful handwashing and chlorination of swimming pools

41. Adenoviral vectors for gene delivery:

42. Generation of adenoviral vectors: E1 Advantages? Disadvantages?

43. 6/016/10 6/15