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Viruses

Obligate Intracellular Parasites: Require living host cell in order to replicate. Genome of a single type of nucleic acid (RNA or DNA; ss or ds) They have no mechanism for NA replication and translation. Must invade and take over host cell’s functions & resources.

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Viruses

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  1. Obligate Intracellular Parasites: • Require living host cell in order to replicate. • Genome of a single type of nucleic acid (RNA or DNA; ss or ds) • They have no mechanism for NA replication and translation. • Must invade and take over host cell’s functions & resources. • Has a protein coat and other specialized structures for attachment to and transferring viral nucleic acid into to the host. Viruses Viral Structure Growing (Cultivating) Prokaryote Types Eukaryote Types

  2. Scale?

  3. Naked Virus Structure Helical Polyhedral Protein coat (capsid) is made of capsomere proteins, who slight mutation may result in new strains of that virus. Capsid protects the nucleic acid genome within. Capsomere protein binds virus to specific sites on the host cell surface.

  4. T-Even Phage Type of bacteriophage (virus of a bacterium). Tail fibers and pins attach virus to specific sites on the host cell surface.

  5. Enveloped Viruses Only some eukaryotic virus types are enveloped. Envelope is plasma membrane from the host cell with viral proteins (e.g. spikes) added into the membrane prior to “budding” out from host cell.

  6. Growing (Cultivating) Viruses Bacteriophage: grow on bacterial “lawns”; will form plaques (clearing zone; this week in lab). Eukaryotic Viruses: grow in tissue culture; plaques form or infected (transformed) cells may look abnormal and clump.

  7. Eukaryotic viruses can also be mass- grown in embryonated chicken eggs.* If you have an egg allergy, be careful of vaccines for enveloped viruses that are manufactured this way.

  8. Bacteriophage Lytic Life Cycle Phage lysozyme is involved.

  9. Viral DNA circularizes then replicates by the: • “Rolling Circle Mechanism” • Nick single strand. • Extend at 3’-OH. • Displace parent strand. • Synthesize complement for displaced strand to get dsDNA. • Long concatemer gets cut into individual phage genomes. This cutting step is what also cuts up the bacterial chromosome.

  10. With many copies of phage genomes, phage genes are expressed to make (biosynthesize) large numbers of phage proteins that then assemble (mature) into new phage particles. Release involves phage enzymes, endolysin and holin, to form holes in the host cell membrane and cell wall.

  11. Time Scale of Lytic Cycle Eclipse Period (= can’t see intact phage particles in cell) Virulent phageonly have a lytic life cycle.

  12. Lysogenic Life Cycle Temperate Phage have both lytic and lysogenic cycles.

  13. Control of lytic versus lysogenic: • Upon penetration of host, a temperate phage immediately expresses a repressor protein. • Most often repressor is produced fast and blocks transcription of lytic genes. • Integrase (viral enzyme) is expressed; facilitates integration at att sites (i.e. lysogeny begins). • Repressor will also block transcription of other invading phage; bacterium with prophage is “protected”. • Under host cell stress, repressor protein degrades; excisionase and other lytic cycle proteins become expressed.

  14. Eukaryotic Viruses • Taxonomy characters: • nucleic acid type; • enveloped or naked; • capsid shape; • assembly site in host (nucleus or cytoplasm)

  15. Attachment and Penetration: • Attachment phase is conceptually similar to phage. • 2) Penetration can be very different from bacteriophage: • - direct penetration by naked virus (like for bacteriophage) • - fusion of enveloped virus with host membrane; capsid enters host cell. • - endocytosis of enveloped virus; followed by fusion of viral envelope with endosome membrane; capsid enters host cell.

  16. NOTE: in both mechanisms the nucleic acid is “uncoated”, i.e. capsid disassembles. Enveloped virus fusing with endosome membrane for release of capsid.

  17. DNA virus Papovavirus (warts) Release by exocytosis Transcription & replication in nucleus; capsid assembly in nucleus!

  18. RNA Virus Types Polio; common cold In the cytoplasm. (RdRp) In the cytoplasm; except influenza

  19. RNA viruses = respiratory enteric orphan viruses In the cytoplasm. In the cytoplasm.

  20. Retrovirus (+RNA)

  21. Infection Types and Outcomes • Acute versus Persistent Infections: • Chronic (replicates at low levels & constant yet mild symptoms) • Latent (stops reproduction after initial infection; goes dormant until induced to activate replication again) • Slow (vary slow replication and spread; years before symptoms) • Cell damage and cytocidal effects (death): • Inhibit host macromolecule synthesis • Lysosome malfunction (host cell self digests) • Plasma membrane disruptions (nutrient transport and communication) • Direct viral protein toxicity • Protein aggregation (inclusion bodies) • Host cell changes to a malignant cell (cancer) • Tumors form by neoplasia and anaplasa; may spread by metastasis. • Virus may carry oncogenes (genes for various cancer causing proteins). • Viral promotors may also insert and turn on expression of host oncogenes or turn off expression of tumor suppression genes.

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