What is a virus?

1. What is a virus? • Obligate intracellular parasite • Small: 10-100 nm • Nucleic acid genome • DNA or RNA • single- or double-stranded • Protein capsid • Lipid envelope for some animal viruses • Enveloped RNA virus Naked DNA virus

2. Viruses don’t divide, they replicate • No metabolism outside a host cell • Requires host nucleotides, amino acids, enzymes, energy • Genome directs host cell to make virus proteins • Copies of genome + proteins assembled into new viruses

3. Is a virus a cell? cells viruses genetic material composition metabolism membrane size

4. Is a virus alive?

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

6. Attachment • Virus protein binds membrane receptor • Determines host range virus “spike” protein host cell receptor host cell receptor virus “spike” protein HPV (naked) influenza virus (enveloped)

7. Entry • Naked virus usually enters by endocytosis • Enveloped virus usually enters by fusion HPV (naked) influenza virus (enveloped)

8. Uncoating • Genome released from capsid proteins • For naked virus, must also escape vesicle HPV (naked) influenza virus (enveloped)

9. Replication • Genome replicated • Viral proteins synthesized by host ribosomes envelope proteins inserted into membrane HPV (naked) influenza virus (enveloped)

10. Assembly • Viral proteins self-assemble into capsid • Viral proteins package genome HPV (naked) influenza virus (enveloped)

11. Exit • Naked virus lyses cell • Enveloped virus “buds” out, taking membrane as envelope HPV (naked) influenza virus (enveloped)

12. 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

13. Antiviral drugs • Acyclovir • Herpes family: herpes, chicken pox, shingles, etc. • Blocks viral DNA synthesis • Reduces duration and severity of infection

14. Antiviral drugs • “Relenza” and relatives • Influenza virus • Prevents new budding viruses from detaching and spreading • Reduces duration of flu by ~2 days

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

16. Vaccination • Our best weapon against viruses so far

17. Vaccination • Inject safe form of viral proteins (antigens) • Immune system produces antibodies and memory cells • Fast response to actual virus prevents disease Y Y Y Y Y Y Y Y Y Y Y antibody production → anti-flu antibodies infection with actual flu virus Y Y Y Y “flu shot” (killed virus) ≈10 days 1-2 days time →

18. 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

19. Vaccination • Polio should be the next disease to be eradicated 1988 350,000 cases 2010 968 cases

20. 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

21. Emerging viral diseases • Mutation • New influenza virus strains (need a shot every year) • “Swine flu” or “Bird flu” becomes human flu pandemic? • Species jump • HIV probably evolved from a chimpanzee virus • SARS coronavirus may have started as a bat virus • Spread from isolated population • Public attention/media