CHAPTER 10

1. CHAPTER 10 Adenovirus

2. Definitions of the virus: • Explant cultures of human adenoids degenerated spontaneously, isolated a new virus named adenovirus. • Adenovirus is the etiological agent of infectious canine hepatitis.

5. Definitions of the virus: • The family Adenoviridae comprises (1) Mastadenovirus: infect mammalian species. (2) Aviadenovirus: infect birds. (3) Atadenovirus: infect broad host range. (4) Siadenovirus: frog, turkey, raptors, budgerigars, and tortoises. (5) Adenovirus of fish: white sturgeon adenovirus

8. INTRODUCTION • Antigenic determinants associated with the inner part of hexons-structural units make up the bulk of the capsid; Hexons involved in neutralization and hemagglutination. • Genus-specific antigen: the basal surface of the penton; serotype-specific antigen: the outward-facing surface of the hexon.

9. INTRODUCTION • Non-enveloped, precisely hexagonal in outline, with icosahedral symmetry, 70-90 nm in diameter. • Virions are composed of 252 capsomers: 240 hexons that occupy the faces and edges of the 20 equilateral triangular facets of the icosahedron and 12 pentons that occupy the verticles. • A penton fiber 9-77.5 nm in length, with a terminal knob.

10. INTRODUCTION • The viral genome encodes approximately 40 proteins that are transcribed after complex RNA splicing. • About one-third of the proteins are structural proteins, including a virus-encoded cysteine protease necessary for processing of some precursor proteins. • Adenoviruses agglutinate red blood cells, with hemagglutination occurring when the tips of penton fibers bind to cellular receptors and form bridges between cells.

11. INTRODUCTION • Adenovirus replicate in the nucleus, and their replication is facilitated by extensive modulation of the host immune response. • Viruses bind to host-cell receptors via their fiber knots and internalization is mediated by the interaction between the penton base and cellular integrins. • The genome is transcribed by cellular RNA polymerase II involving both DNA strands.

12. INTRODUCTION • Five early (E) transcriptional units (E1A, E1B, E2, E3, and E4), two intermediate units (IX and IVa2), and one late (L) unit from which five families of late mRNA (L1 to L5) are transcribed. • Each early region is controlled by a separate promoter, whereas the late region uses the major late promoter. • The E1A region encodes proteins for (1) induction of cell-cycle progression to provide an environment for virus replication; (2) protection of infected cells from cytokine-induced apoptosis; (3) synthesis of viral proteins necessary for viral DNA replication.

13. INTRODUCTION • E1A and E1B proteins inactivate the cellular tumor suppresser gene, p53, and thus deregulate cell-cycle progression. • Inactivation is mediated by ubiquitination of p53 and other proteins through virus-assembled E3 ligases, leading to proteasome-mediated degradation. • Inhibition of class I MHC antigen transport by E3/19K inhibits recognition of infected cells by cytotoxic T lymphocytes and NK cells. • E3/14.7K blocked TNF alpha receptor and inhibited NF-κB transcriptional activity.

14. INTRODUCTION • Viral DNA replication, using 5’-linked 55K protein as primer, proceeds from both ends by a strand-displacement mechanism. After DNA replication, late mRNAs are transcribed; these are translated into structural proteins. • The primary transcript is about 29 kb; at least 18 distinct mRNA are produced by alternative splicing. • Many adenoviruses cause severe condensation and margination of the host-cell chromatin, making nuclei appear abnormal (inclusion bodies).

16. Papillomaviridae

17. Definitions of the virus: • Papillomaviruses are the cause of papillomas (warts). • Papillomaviruses can not yet be grown in conventional cell cultures, but their genome readily be sequenced.

19. Definitions of the virus: • Papillomaviruses are ubiquitous, but individual viruses are host-species specific. • Pathogenic papillomavirus infections occur with some frequency in psittacine birds.

20. INTRODUCTION • The papillomaviridae family includes viruses with circular double-stranded DNA genomes. • There is little sequence homology between the genomes of papillomaviruses from different species.

21. INTRODUCTION

22. INTRODUCTION • The papillomaviridae family includes viruses with circular double-stranded DNA genomes. • Bovine papillomaviruses are genetically divergent. In dogs, papillomaviruses are the cause of epithelial plaques and papillomas of the skin and mucosal lining of the

23. INTRODUCTION of the oral cavity, conjunctiva, and external genitalia. • Papillomavirus virions are non-enveloped, spherical, 55 nm in diameter, with icosahedral symmetry. • The genome consists of a single molecule of circular double-stranded DNA, 6.4-8.4 kb.

24. INTRODUCTION • The genome encodes 8-10 proteins, two of which (L1 and L2) form the capsid. The E1-E8 are non-structural proteins which exert regulatory and replicative functions. • Papillomaviruses are resistant to environmental insults.

27. INTRODUCTION • Replication is linked to the growth and differentiation of stratified squamous epithelium of the skin and mucous membranes. • Actively dividing basal cells in the stratum germinativum are infected initially, and the virus is maintained in a proviral, latent state .

28. INTRODUCTION • Virus-induced hyperplasia (early virus gene products) leads to increased basal cell division and delayed maturation of cells in stratum spinosum and granulosum. • Late viral genes encoding capsid proteins in stratum spinosum and

29. INTRODUCTION and virions appear at this stage of cellular differentiation. • The heparan sulfate proteoglycan and syndecan-3 can serve as a human papillomavirus receptor on dendritic cells. • Transcription of early and late coding region is controlled by

30. INTRODUCTION separate promoters and occurs on the same DNA strand. • First, the half of the genome (the early genes) is transcribed to form mRNAs that direct the synthesis of enzymes involved in virus replication and cell regulation. • Late mRNAs that direct the synthesis of the structural proteins

31. INTRODUCTION (L1 and L2) involved in capsid assembly which are transcribed from the other half of the viral genome. • The regulated expression of the late (L1 and L2) proteins occurs only in differentiated epithelial cells or in differentiating keratinocytes.

32. INTRODUCTION • DNA replication begins at a single unique origin of replication (ori) and proceeds bidirectionally on the circular DNA. • An initiation complex binds to the origin and unwinds a region; nascent DNA chains are formed, one strand being synthesized

33. INTRODUCTION • DNA replication begins at a single unique origin of replication (ori) and proceeds bidirectionally on the circular DNA. • An initiation complex binds to the origin and unwinds a region; nascent DNA chains are formed, one strand being synthesized

34. INTRODUCTION continuously in the direction of unwinding, the other synthesized discontiously in the opposite direction. • It encodes a specific viral helicase. • Virions are assembled in the nucleus and are released on cell death, a consequence of cellular

35. INTRODUCTION obsolescence. A infected cell may produce 10000 to 100000 virions. • E6 protein is a key component which is a transcriptional activator, and interacts with and inhibits or degrades a variety of cellular proteins, including the transcription activator, CBP/p300 and p53 tumor suppressor.

36. INTRODUCTION • It interacts with activating protein 1 in trans-Golgi processes, and it blocks the activity of paxillin, that contributes to focal adhesions between cells. • The host immune response to papillomavirus infection is directed against the virus, affording

37. INTRODUCTION protective immunity to subsequent infection, and against the virus-induced tumor, resulting in regression of the papilloma or fibropapilloma. • Once an animal is immune to virus or has undergone tumor regression, it is strongly resistant to reinfection, but it is virus-strain specific.

39. Polyomaviridae

40. Definitions of the virus: • Polyomaviruses have highly restricted host ranges, and these viruses typically cause life-long, inapparent infections in their respective hosts. • The family Polyomaviridae contains

41. Definitions of the virus: • Polyomaviruses have highly restricted host ranges, and these viruses typically cause life-long, inapparent infections in their respective hosts. • The family Polyomaviridae contains a single genus, Polyomavirus.

42. Definitions of the virus: • The genome organization, virion structure, and replication strategy of polyomaviruses is generally similar to that of papillomviruses. • Virions and the genome (5 kb) are smaller than those of papillomaviruses.

43. Definitions of the virus: • The transcription of coding regions occurs on opposite DNA strands in polyomaviruses and on the same strand with papillomaviruses. • Polyomaviruses regulate the cell cycle and transform infected cells through their non-structural proteins.

44. Definitions of the virus: • Transformation of infected cells occurs by specific inactivation of the cellular p53 tumor suppressor gene. • Reactivation of persistent, latent polyomavirus infections occurs as a consequence of immunosuppression, potentially as a result of mutations in the transcriptional control region.