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VIRUSES ENCODE INFORMATION FOR

VIRUSES ENCODE INFORMATION FOR. ENSURING GENOME REPLICATION ENSURING GENOME PACKAGING ALTERATION OF STRUCTURE AND/OR FUNCTION OF THE HOST CELL. STRATEGY. WAY IN WHICH VIRUS CARRIES OUT THESE FUNCTIONS look out for weak points. INTRACELLULAR PARASITES. NEED TO OBEY RULES

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VIRUSES ENCODE INFORMATION FOR

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  1. VIRUSES ENCODE INFORMATION FOR • ENSURING GENOME REPLICATION • ENSURING GENOME PACKAGING • ALTERATION OF STRUCTURE AND/OR FUNCTION OF THE HOST CELL

  2. STRATEGY • WAY IN WHICH VIRUS CARRIES OUT THESE FUNCTIONS • look out for weak points

  3. INTRACELLULAR PARASITES • NEED TO OBEY RULES • OR BE ABLE TO BEND THE RULES Nucleus (SV40) cytoplasm (a paramyxovirus) Hsiung and Fong, from Hsiung’s Diagnostic Virology 1994

  4. DNA VIRUSES • mRNAs needed to make proteins • host has a DNA-dependent RNA polymerase, plus the additional proteins need to make properly modified mRNA • need to replicate their DNA • host has a DNA polymerase, plus the additional proteins needed to replicate DNA • HOST MACHINERY IS IN THE NUCLEUS

  5. CYTOPLASMIC DNA VIRUSES • need to code for cytoplasmic DNA and RNA polymerases • need to code for accessory proteins needed for DNA and RNA synthesis • will have large genomes • poxvirus family (30-75 times genome size of the smallest nuclear DNA viruses – parvoviruses and polyomaviruses)

  6. DNA genome sizes (# bases) • Parvoviruses 5 kb • Polyoma 5 kb • Papilloma 8 kb • Adenoviruses 30-42 kb • Herpesviruses 120-200 kb • Poxviruses 130-375 kb • E.coli 4700 kb

  7. PARVOVIRUSES • SMALL DNA VIRUSES • parvo = small (18-25nm) • SINGLE STRAND DNA • 5 kilobases (5000 nucleotides) • REPLICATE DNA IN NUCLEUS • Human B19 parvovirus infects dividing cells (primarily erythroid progenitors) • ICOSAHEDRAL SYMMETRY

  8. PAPILLOMAVIRUSESPOLYOMAVIRUSES • small (40-60nm) • icosahedral capsid • mainly VP1 • some VP2, VP3 • non enveloped • ds DNA (circular) • associated with histones • genome • Papilloma 8 kb (kilobases) • Polyoma 5 kb human papillomavirus Murray Fig. 49.1

  9. PAPILLOMA VIRUSES WARTS SOME PAPILLOMA VIRUSES ARE ASSOCIATED WITH CANCER human papillomavirus Murray Fig. 49-4

  10. POLYOMAVIRUSES PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) TUMORS IN ANIMALS http://medstat.med.utah.edu/WebPath/TUTORIAL/AIDS/AIDS.html#10

  11. P H POLYOMAVIRUS FAMILY • POLYOMA VIRUS • SV40 VIRUS • BK VIRUS • JC VIRUS • LYTIC CYCLE • NON-LYTIC CYCLE

  12. ADSORPTION, PENETRATIONUNCOATING OUTSIDE ds DNA + histones NUCLEUS CYTOPLASM 17

  13. LYTIC CYCLE • EARLY PHASE - GENERAL • PROTEINS NEEDED FOR DNA REPLICATION • REGULATORY PROTEINS • OFTEN PROTEINS WHICH ALTER HOST CELL • LATE PHASE - GENERAL • DNA REPLICATION • NEW STRUCTURAL PROTEINS

  14. poly(A) tail A A A T antigen t antigen EARLY mRNA SYNTHESIS 0 20 80 DNA 60 40 SV40 (polyoma virus) modified from Fiers et al., Nature 273:113

  15. 0 0 0 0 20 20 20 20 80 80 80 80 DNA DNA DNA DNA 60 60 60 60 40 40 40 40 T antigen HOST DNA REPLICATION MACHINERY HOST CELL HISTONES DNA SYNTHESIS SV40 (polyoma) virus

  16. the power of two!

  17. T antigen HOST CELL HISTONES 0 20 80 DNA 60 40

  18. VP1 A A A VP3 A VP2 T antigen 0 20 80 DNA 60 40 LATE mRNA SYNTHESIS SV40 (polyoma virus) modified from Fiers et al., Nature 273:113

  19. VP1 VP3 VP2 A A A A 0 80 DNA 20 60 40 NH2 - met - ala - pro - thr - lys - ..... VP1 G A U G G C C C C A A C A A A A . . . . . . . asp - gly - pro - asn - lys - ...... VP2, VP3

  20. 0 20 80 0 20 60 40 80 DNA 60 40 ROLES OF LARGE T ANTIGEN • DNA replication

  21. 0 20 80 0 20 60 40 80 DNA 60 40 ROLES OF LARGE T ANTIGEN • DNA replication • increased transcription of late genes

  22. 0 A A 20 80 0 20 60 40 80 DNA 60 40 ROLES OF LARGE T ANTIGEN • DNA replication • increased transcription of late genes

  23. 0 A A 20 80 0 20 60 40 80 DNA 60 40 ROLES OF LARGE T ANTIGEN A • DNA replication • increased transcription of late genes • decreased transcription of early genes A

  24. 0 A A A 20 80 0 20 60 40 80 DNA 60 40 ROLES OF LARGE T ANTIGEN • DNA replication • increased transcription of late genes • decreased transcription of early genes A

  25. T-antigen interacts with cellular proteins ROLES OF LARGE T ANTIGEN • DNA replication • increased transcription of late genes • decreased transcription of early genes • cellular transformation

  26. ASSEMBLY • NUCLEUS • CAPSID PROTEINS • HISTONES • inclusion bodies

  27. RELEASE • CELL LYSIS

  28. A VP1 A A VP3 A A A VP2 A 0 20 80 DNA 60 40 t antigen T antigen SOME FEATURES TO NOTE • early and late functions • multiple use of the same DNA sequence • multifunctional protein • small genome - few proteins • host cell provides • DNA synthesis machinery • RNA synthesis machinery • histones modified from Fiers et al., Nature 273:113

  29. ADENOVIRUSES • linear, double stranded DNA (30-42 kb) • non-enveloped • icosahedral • 70nm diameter http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/em_adeno.gif

  30. ADENOVIRUSES • upper respiratory tract infections • conjunctivitis • gastrointestinal infections • cystitis • tumors in some animals

  31. ADENOVIRUS VIRION A • more proteins • more hexons • linear DNA • no histones http://www.embl-heidelberg.de/ExternalInfo/fuller/ad2fb.gif Fields et al., Fundamental Virology, 1996

  32. ADSORPTION, PENETRATION, UNCOATING Zinsser Microbiology 20th Ed.

  33. EARLY mRNA SYNTHESIS Adapted from Broker,T.R. In Processing of RNA. (Apirion, D ed) 181-212, 1984

  34. immediate early Early proteins include proteins which: • are needed for transcription of other early mRNAs • E1a gene product • are needed for DNA synthesis • alter expression of host genes • interfere with the host anti-viral defenses • interfere with cell cycle regulation Adapted from Broker,T.R. In Processing of RNA. (Apirion, D ed) 181-212, 1984

  35. 5’ 5’ 3’ 3’ 3’ 3’ 5’ 5’ DNA REPLICATION

  36. 5’ 5’ 5’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 3’ 5’ 3’ 3’ 5’ 5’ 3’ 5’ 5’ 5’ 3’ 3’ 3’ 3’ 5’ 3’ 5’ 3’ 5’ 5’ 3’ 3’ 5’ 3’ 5’ DNA REPLICATION

  37. 5’ 5’ 5’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 3’ 5’ 3’ 3’ 5’ 5’ 3’ 5’ 5’ 5’ 3’ 3’ 3’ 3’ 5’ 3’ 5’ 3’ 5’ 5’ 3’ 3’ 5’ 3’ 5’ DNA REPLICATION = terminal protein (TP)

  38. 5’ 5’ 5’ 3’ 3’ 3’ 3’ 3’ 3’ 3’ 5’ 5’ 5’ 5’ 5’ 5’ 5’ 3’ 5’ 3’ 3’ 5’ 5’ 3’ 5’ 5’ 5’ 3’ 3’ 3’ 3’ 5’ 3’ 5’ 3’ 5’ 5’ 3’ 3’ 5’ 3’ 5’ DNA REPLICATION single strand binding protein

  39. Adapted from Broker,T.R. In Processing of RNA. (Apirion, D ed) 181-212, 1984

  40. AAAAAAAA monocistronic mRNA problem mRNA AAAAAAAA RIBOSOMES PROTEIN

  41. AN EXAMPLE OF PROCESSING: H primary transcript H cut at poly(A) site H polyadenylate AAAAAAAA H intron removal AAAAAAAA AAAAAAAA H hexon mRNA

  42. ASSEMBLY • assemble in nucleus • maturation stage • release by cell lysis • excess structural proteins Koneman et al. Color Atlas and Textbook of Diagnostic Microbiology 5th Ed. 1997

  43. SOME FEATURES TO NOTE ABOUT ADENOVIRUSES • larger and more complex than papovaviruses • code for their own DNA polymerase and DNA packaging proteins • early genes scattered, late genes in a block • host cell provides • DNA synthesis accessory factors • RNA synthesis and modification enzymes • so not surprising that go to nucleus

  44. Adapted from Broker,T.R. In Processing of RNA. (Apirion, D ed) 181-212, 1984

  45. glycoprotein spikes = peplomers tegument lipid bilayer HERPESVIRUSES icosahedral nucleocapsid nucleocapsid from: http://hub.med.uth.tmc.edu/~hong/image.html

  46. HERPESVIRUSES • LARGE GENOME • polyoma 5 kb • adeno 30-42 kb • herpes 120-220 kb • herpes simplex viruses • Epstein Barr virus • chicken pox/shingles – varicella (herpes) zoster virus • cytomegaloviruses electron micrograph by Linda Stannard: http://www.uct.ac.za/depts/mmi/stannard/emimages.html

  47. herpesviruses, paramyxoviruses, HIV

  48. INFECTED CELL UNINFECTED CELL

  49. INFECTED CELL UNINFECTED CELL

  50. INFECTED CELL UNINFECTED CELL

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