1.  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 What is a virus? Enveloped RNA virus Naked DNA virus

2.  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 Viruses don’t divide, they replicate

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

4. Is a virus alive? livingnon-living

5. 1. Attachment 2. Entry 3. Uncoating 4. Nucleic acid replication & protein synthesis 5. Assembly 6. Exit Virus replication

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

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

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

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

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

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

12.  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 Antiviral drugs

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

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

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

16.  Our best weapon against viruses so far Vaccination

17.  Inject safe form of viral proteins (antigens)  Immune system produces antibodies and memory cells  Fast response to actual virus prevents disease Vaccination “flu shot” (killed virus) Y Y Y Y anti-flu antibodies antibody production → time → ≈10 days1-2 days infection with actual flu virus Y Y Y Y Y Y Y Y Y Y Y

18.  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 Smallpox vaccination

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

20.  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 Vaccine issues

21.  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 Emerging viral diseases