1. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 1 Chapter 18 Eucaryotic Viruses and Other Acellular Infectious Agents

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2 Taxonomy of Eucaryotic Viruses most of the ~5,000 known viruses infect eucaryotic organisms Characteristics used for virus classification by the ICTV –Genome structure –Replication strategy –Morphology –Genetic relatedness

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 3 Taxonomy of Eucaryotic Viruses can be naked (lack an envelope) or enveloped nucleic acid can be single or double stranded DNA or RNA Some have segmented genomes made of more than one distinct nucleic acid molecule

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 4 Viruses that Infect Vertebrates Figure 18.1

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 5 Taxonomy of DNA Animal Viruses Figure 18.2

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 6 Taxonomy of RNA Animal Viruses Figure 18.3

7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 7 Reproduction of Animal Viruses adsorption penetration and uncoating replication of virus nucleic acids synthesis and assembly of virions virion release

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 8 Adsorption tropism displayed by vertebrate viruses –virions attach to host cells displaying the proper receptor

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 9 Table 18.1

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 10 Penetration and Uncoating one of two mechanisms used by most viruses –fusion of envelope with host cell membrane –endocytosis in some cases only nucleic acid enters host cell

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 11 Fusion with host membrane Figure 18.4 (a)

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 12 Endocytosis – enveloped virus Figure 18.4 (b)

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 13 Endocytosis – naked virus Figure 18.4 (c)

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 14 Genome Replication and Transcription in DNA Viruses early genes –encode proteins involved in take over of host and in synthesis of viral DNA and RNA viral DNA replication –usually occurs in nucleus early mRNA synthesis –usually by host RNA polymerase

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 15 e.g., parvoviruses single-stranded DNA (ssDNA) viruses small genomes with overlapping genes –only encode capsid proteins use host enzymes for all biosynthetic processes –viral DNA only replicated during S period of cell cycle

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 16 Secondary Structure of the Parvovirus ssDNA Genome Figure 18.5

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 17 e.g., herpes simplex virus I uses host RNA polymerase for synthesis of viral mRNA uses virus- encoded DNA polymerase for replication of genome Figure 18.6

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 18 e.g., poxviruses large, morphologically complex double-stranded DNA (dsDNA) viruses virion carries DNA-dependent RNA polymerase that synthesizes early mRNA –encodes DNA polymerase and other enzymes needed for DNA replication

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 19 e.g., hepadnaviruses circular, dsDNA genome genome transcribed by host RNA polymerase –generates several mRNA molecules one is large RNA (pregenome) others encode polymerase with reverse transcriptase activity pregenome converted to dsDNA by virus polymerase

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 20 Gapped Genome of Hepadnaviruses Figure 18.7

21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 21 Genome Replication, Transcription, and Protein Synthesis in RNA Viruses very diverse reproductive strategies four general modes of replication and transcription

22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 22 Figure 18.8

23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 23 Assembly of Virus Capsids late genes direct capsid protein synthesis which spontaneously self-assemble to form the capsid during icosahedral virus assembly empty procapsids form first, nucleic acid are then inserted assembly of envelope viruses –in most cases, similar to assembly of naked viruses site of morphogenesis varies

24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 24 Figure 18.2

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 25 Crystalline Assay of Adenoviruses Within the Nucleus Figure 18.10

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 26 Virion Release all viral envelopes are derived from host cell membranes in multistep process naked viruses –usually by lysis of host cell envelope viruses –formation of envelope and release usually occur concurrently virus-encoded proteins incorporated into host membrane nucleocapsid buds outward and is surrounded by modified host membrane

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 27 Release of influenza virus by budding Figure 18.11

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 28 HIV release by budding Figure 18.12 (a)

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 29 Figure 18.12 (b)

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 30 Virion release… many viruses use host actin filaments to aid release process

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 31 Cytocidal Infections and Cell Damage cytocidal infection –infection that results in cell death

32. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 32 Mechanisms of host cell damage and cell death inhibition of host DNA, RNA, and protein synthesis lysosome damage –causes release of hydrolytic enzymes into cell alteration of plasma membrane –can lead to attack of host cell by immune system –can lead to cell fusion, forming syncytium

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 33 Other mechanisms… toxicity from high concentrations of viral proteins formation of inclusion bodies –can disrupt cell structure chromosomal disruptions transformation of host cell into malignant cell

34. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 34 Persistent, Latent, and Slow Virus Infections acute infections –rapid onset and relatively short duration persistent infections –can last many years

35. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 35 Types of persistent infections chronic virus infection –virus almost always detectable –clinical symptoms mild or absent for long periods latent virus infection –virus stops reproducing and remains dormant for some time –during latency, symptoms, antivirus- antibodies, and viruses are not detectable

36. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 36 Possible causes of persistent infections integration of viral genome into host genome decrease in antigenicity of virus mutation to less virulent and slower reproducing form –defective interfering (DI) particle – deletion mutant that cannot reproduce and slows reproduction of normal virus

37. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 37 Types of Infections and Their Effects on Host Cells Figure 18.13

38. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 38 Slow virus diseases symptoms take years to emerge e.g., subacute sclerosing panencephalitis caused by measles virus e.g., HIV infections

39. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 39 Viruses and Cancer tumor –growth or lump of tissue neoplasia –abnormal new cell growth and reproduction due to loss of regulation anaplasia –reversion to a more primitive or less differentiated state metastasis –spread of cancerous cells throughout body

40. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 40 Carcinogenesis complex, multistep process often involves oncogenes –cancer-causing genes –many involved in regulation of cell growth and differentiation some viruses contribute to carcinogenesis

41. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 41 Viruses implicated in human cancers Epstein-Barr virusBurkitt’s lymphoma nasopharyngeal carcinoma Hepatitis B virusliver cancer Hepatitis C virusliver cancer Human herpesvirus 8 HIV Kaposi’s sarcoma human papillomaviruscervical cancer HTLV-1 and HTLV-2leukemia

42. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 42 Possible mechanisms by which viruses cause cancer carry oncogene into cell and insert it into host genome altered cell regulation due to changes in kinase activity or production of regulatory proteins insertion of promoter or enhancer next to cellular oncogene

43. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 43 Plant Viruses cause variety of plant diseases not as well studied as bacteriophages and animal viruses

44. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 44 Plant Virus Taxonomy most are RNA viruses Figure 18.14

45. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 45 Virion Morphology does not differ significantly from that of animal or bacterial viruses turnip yellow mosaic virus Figure 18.15

46. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 46 Plant Virus Reproduction virus penetration of host is hampered by complex outer layers of plant host entry of virus requires mechanical damage, usually caused by insects or animals that feed on host most plant viruses are RNA viruses –most of these are plus-strand RNA

47. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 47 Plant Virus Reproduction e.g., tobacco mosaic virus (TMV) –filamentous, plus strand RNA virus –RNA replication unclear if catalyzed by host RNA- dependent RNA polymerase or virus encoded enzyme –protein synthesis processed viral genome serves as mRNA –new virions assemble spontaneously

48. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 48 TMV assembly Figure 18.16

49. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 49 intracellular TMV Figure 18.17

50. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 50 Viruses of Fungi and Protists fungal viruses –higher fungi infected with dsRNA viruses –most cause latent infections –lower fungi infected by dsRNA or ssRNA viruses –cause lysis algal viruses –the 4 genera recognized by ICTVhave linear dsDNA genomes protozoan viruses –viruses of only 3 genera have been studied –giant dsDNA virus (tentative named a Mimivirus) found in Acanthamoeba polyphaga

51. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 51 Insect Viruses belong to many virus families infection often accompanied by formation of granular or polyhedral inclusion bodies have potential as biological control agents for insect pests

52. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 52 Inclusion Bodies Figure 18.18

53. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 53 Viroids and Virusoids viroids –infectious agents composed only of RNA virusoids –formerly called satellite RNAs –infectious RNAs that encode one or more gene products –require a helper virus for replication

54. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 54 Viroids, Viruses and Bacteria Figure 18.19

55. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 55 Viroids cause plant diseases are covalently closed, circular, single- standed RNAs, ~250-370 nucleotides long –has rodlike shape due to intrastrand base pairing some found in infected host cell nucleolus, others found in chloroplast

56. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 56 Viroid Structure Figure 18.20

57. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 57 More about Viroids… unable to replicate itself because its RNA does not encode gene products –may be replicated by a host DNA- dependent RNA polymerase –RNA synthesis may use a rolling circle- like mechanism may cause disease by triggering RNA silencing

58. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 58 Virusoids –like viroids are covalently closed circular, ssRNA molecules capable of intrastand base paring –unlike viroids they encode one or more gene products and need a helper virus to infect host cells

59. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 59 Prions – Proteinaceous Infectious Particle examples of degenerative diseases in animals caused by prions –scrapie –bovine spongiform encephalopathy (BSE) or mad cow disease –Creutzfeldt-Jakob disease (CJD) and varient CJD (vCJD) –kuru

60. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 60 Current Model of Disease Production by Prions PrP C (prion protein) is present in “normal” form in host and abnormal form of prion protein is PrP Sc entry of PrP Sc into animal brain causes PrP C protein to change its conformation to abnormal form. the newly produced PrP Sc molecules then convert more normal molecules to the abnormal form interactions between PrP Sc and PrP C may result in the crosslinking of PrP C molecules resulting in neuron loss

61. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 61 What about Mad Cow Disease? prions cause bovine spongiform encephalopathy (BSE or mad cow disease) epidemic proportions in England in 1990s initially spread because cows were fed meal made from all parts (including brain tissue) of infected cattle

62. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display 62 Variant Creutzfeldt-Jakob (vCJD) v. CJD difference in diseases is origin –eating meat from BSE infected cattle can cause variant Creutzfeldt-Jakob (vCJD) in humans –CJD is caused by spontaneous mutation of the gene that codes the prion protein all prion caused diseases –have no effective treatment –result in progressive degeneration of the brain and eventual death