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Polio

Smallpox. Tobacco mosaic virus infection. Polio. Herpes simplex type 2 infection. Mumps. Potyvirus infection. Bacteriophage. VIRUSES CAUSE DISEASE. What is a virus?. - Obligate intracellular parasite -Small: 10-100 nm -Structure -Nucleic acid genome -Protein capsid

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Polio

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  1. Smallpox Tobacco mosaic virus infection Polio Herpes simplex type 2 infection Mumps Potyvirus infection Bacteriophage VIRUSES CAUSE DISEASE

  2. What is a virus? -Obligate intracellular parasite -Small: 10-100 nm -Structure -Nucleic acid genome -Protein capsid -Lipid envelope for some animal viruses “spike” capsid Enveloped viruses Nonenveloped viruses

  3. Virus replication: Problem What is needed for virus replication: Protein synthesis DNA replication PROBLEM: Small genome

  4. Virus replication: Solution • - Virus infects a host cell in order to replicate • -no metabolism outside the host cell • -requires host nucleotides, amino acids, enzymes, energy • Viral genome directs host cell to make viral proteins • - Copies of genome + proteins assembled into new viruses

  5. What is a virus? Viruses are noncellular, nonliving infectious particles consisting of a genome surrounded by a protein coat.

  6. Is a virus a cell? cells viruses genetic material dsDNA DNA or RNA, ds or ss composition nucleic acids (DNA and RNA) 1000s of proteins carbohydrates lipids nucleic acid (DNA or RNA) capsid proteins (1-10s) lipid envelope (some animal viruses) metabolism enzymes break down sugars for energy synthesize DNA, proteins, etc. no active enzymes no energy generation no synthesis of molecules membrane always present essential for transport no functional membrane no transport size 1-10 μm for prokaryotes 10-100 μm for eukaryotes 10-100 nm (similar to ribosome size) A virus does not qualify as a cell.

  7. What is a virus? Viruses are noncellular, nonliving infectious particles consisting of a genome surrounded by a protein coat.

  8. Is a virus alive? • Some characteristics of living things • Most consider viruses non-living

  9. What is a virus? Viruses are noncellular, nonliving infectious particles consisting of a genome surrounded by a protein coat.

  10. What organisms and host cells do viruses infect?

  11. Virus replication • Attachment • Entry • Uncoating • Nucleic acid replication & protein synthesis • Assembly • Exit

  12. Attachment -Virus protein binds membrane receptor -Determines host range virus “spike” protein host cell receptor host cell receptor virus “spike” protein Adenovirus (naked) Influenza virus (enveloped)

  13. Entry -Naked virus usually enters by endocytosis/ followed by endosomal membrane lysis -Enveloped virus usually enters by fusion with the plasma membrane or the endosomal membrane Adenovirus (naked) Influenza virus (enveloped)

  14. Uncoating -Genome released from capsid proteins Adenovirus (naked) Influenza virus (enveloped)

  15. Replication -Genome replicated -Viral proteins synthesized by host ribosomes envelope proteins inserted into membrane Adenovirus (naked) influenza virus (enveloped)

  16. Assembly -Viral proteins self-assemble into capsid -Viral proteins package genome Adenovirus (naked) Influenza virus (enveloped)

  17. Exit -Naked virus lyses cell -Enveloped virus “buds” out, taking membrane as envelope Adenovirus (naked) influenzavirus (enveloped)

  18. Viruses are very diverse Tobacco mosaic virus (plant virus): naked ssRNA genome helical capsid Bacteriophage T4 (bacterial virus): naked dsDNA genome complex capsid Poliovirus (replicating in cell): naked ssRNA genome icosahedral capsid Influenza virus: enveloped ssRNA genome helical capsid

  19. How are viruses classified? Helical: Marburg virus • Enveloped vsNonenveloped • Genetic material • DNA (single stranded or double stranded) • RNA (single stranded or double stranded) • Capsid structure • Helical (rod shape) • Icosahedral • Complex Icosahedral: Adenovirus Complex: Bacteriophage

  20. How is viral infection treated? • For a bacterial infection, a doctor can prescribe antibiotics which kill the bacteria. • For a viral infection: rest, fluids, aspirin, etc. Why are there so few options for treating a viral illness?

  21. Antiviral drugs • Useful drugs must be selectively toxic: • Kill the disease-causing organism • Leave host cells unharmed • Antibiotics exploit differences between proks and euks: • Unique cell wall carbohydrates in bacteria • Unique structures of bacterial ribosomes • Prokaryotic RNA polymerase • Viruses replicate in our own cells, using our own machinery

  22. Targets for antiviral drugs Nonenveloped virus Enveloped virus

  23. Targets for antiviral drugs • Acyclovir • -Herpes family: herpes, chicken pox, shingles, etc. • -Blocks viral DNA synthesis • -Reduces duration and severity of infection

  24. Targets for antiviral drugs • Relenza • -Influenza virus • -Prevents new budding viruses from detaching and spreading • -Reduces duration of flu by ~2 days

  25. Antiviral drugs • HAART “cocktail” • HIV virus • Blocks 2 key viral enzymes • Extends life • Improves quality of life

  26. There are no drugs todaythat can cure any viral disease.

  27. Vaccination • Our best weapon against viruses so far

  28. Vaccination • Inject safe form of viral proteins (antigens) • Immune system produces antibodies and memory cells • Fast response to actual virus prevents disease

  29. Smallpox vaccination • Smallpox killed 300,000,000 in the 20th century • Edward Jenner developed vaccination in 1796 • Vaccination allowed eradication of the disease • Last case in 1977

  30. Vaccination • Polio should be the next disease to be eradicated 1988 350,000 cases 2009 1,595 cases

  31. Vaccine issues • Vaccine development difficult for some diseases (e.g., HIV) • Difficulty of universal distribution • Side effects, real and imagined • Public resistance to vaccination • Sensational, irresponsible media coverage • Not an economic priority for many drug companies • Regulatory issues: >10 years to license a new vaccine

  32. Where do “new” viruses come from?

  33. Emerging viral diseases • Mutation • New influenza virus strains (need a shot every year) • “Swine flu” or “Bird flu” becomes human flu pandemic? • influenza hemagglutinin

  34. Emerging viral diseases • Species jump • HIV probably evolved from a chimpanzee virus • SARS coronavirus may have started as a bat virus • SARS coronavirus

  35. Emerging viral diseases • Spread from isolated population • Public attention/media

  36. VIRUSES USED TO TREAT DISEASE GENETIC DISEASE Ex: Hemophilia A/B, Duchenne muscular dystrophy, cystic fibrosis Problem: Failure to produce a certain protein Solution: Viral vectors used to deliver the gene encoding the missing protein

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