Viruses of Eukaryotes

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Viruses of Eukaryotes

• Animal Viruses

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Diversity of viruses
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DNA virus families
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RNA virus families
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Adsorption

• Binding to specific cell surface receptor
• Protein or carbohydrate residue on protein
• Varied, important functions
• Receptor distribution influences host range
• Some viruses (e.g., HIV) use more than one
  receptor (together)

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Entry

• 1. Direct penetration of viral genome (naked
  virions only)

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Entry

• 2. Direct fusion with plasma membrane (enveloped
  virions only)

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Entry

• 3. Receptor-mediated endocytosis (naked or
  enveloped virions)

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Entry

• 1. Direct penetration of viral genome (naked
  virions only)
• 2. Direct fusion with plasma membrane (enveloped
  virions only)
• 3. Receptor-mediated endocytosis (naked or
  enveloped virions)
• 4. Conformational changes in virion proteins
  releases genome or nucleocapsid

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Replication strategies for RNA viruses

• 1. sense ssRNA (poliovirus) copied by viral
  replicase to make /- double stranded replicative
  form, template for new genome copies

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Replication strategies for RNA viruses

• 2. dsRNA (rotavirus) transcribed by virion
  transcriptase to form sense mRNA, template for
  strand

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Replication strategies for RNA viruses

• 3. - sense ssRNA copied by virion transcriptase
  to make mRNA and ds replicative form

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Replication strategies for RNA viruses

• 4. sense ssRNA reverse transcribed to dsDNA,
  integrates into host chromosome, transcribed by
  host RNA polymerase

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Problem How does an RNA virus encode multiple
proteins?

• Polyprotein (poliovirus)
• Segmented genome (rotavirus)
• Internal transcriptional starts (paramyxovirus)
• RNA splicing (influenza)
• Translational frameshift (retrovirus)
• Ambisense RNA (arenavirus)
• Combinations of above

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The DNA replication problem

• DNA replication requires 5 primer
• Living cells use RNA primers that are later
  removed by nick translation joining of Okazaki
  fragments (chromosome ends have telomeres)
• Failure to replicate 5 end would lead to loss of
  genetic information

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Virus solutions to the 5 end problem

• Circular genome permits removal of Okazaki
  fragments (polyomavirus)
• Fold back ends prime opposite strand (parvovirus)
• Concatemers joined end to end (herpesvirus)
• Protein priming of DNA synthesis (adenovirus)

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Assembly and Release

• Late genes direct production of capsid proteins
• Paracrystalline arrays of particles within cell
• Viral genome has packaging sequence
• Most naked viruses induce cell lysis
• Enveloped particles bud from membrane

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Cellular Damage

• Inhibition of host cell function
• Decapitation, incapacitation
• Release of hydrolytic enzymes from lysosomes
• Membrane defects (syncytia, receptor modulation)
• Toxic proteins (cytokine release)
• Inclusion bodies
• Chromosomal aberrations
• Transformation/tumorigenesis

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Persistent and Latent Infections

• Sequestration in immunolgically protected site
• Decreased expression of viral proteins
• Mutant viruses
• May be mediated by specific virus proteins
  (herpes viruses)

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Viruses and Cancer

• Action of specific viral proteins
• Capture and alteration of host growth controlling
  genes
• Induction of DNA rearrangements