1. HIV and Viruses Lucy Stacey Christella

2. Viruses  Obligate parasites of living cells  Can’t replicate without living host cell  Due to RNApol, ribosomes, etc. are “dumb” – can’t tell viral genes from host cell genes  Host specific – different viruses infect protozoa, plants, animals, etc.

3. Viruses  Goal: turn cell into “virus factory” 1. Virus binds to protein on surface of host cell 2. Virus injects genome into cell 3. Viral proteins made by host’s ribosomes 4. Viral genome copied by host’s enzymes 5. Viruses assemble and leave cell 6. Repeat

4. Minimal Virus Genome 1. Gene for capsid protein 2. Gene for replicating enzyme (if genome isn’t ds DNA) 3. Genes for proteins to release virus from cell 4. Genes to suppress host genes

5. Retroviruses  A single-stranded RNA genome  Normally: DNA -> RNA -> Protein  Retroviruses: DNA Protein  Examples: HIV, feline leukemia virus, etc.

6. Retroviruses  Virus makes a DNA copy of RNA genome (“Retro”)  Virus inserts copy into host’s enzyme  Therefore, virus passed to daughter cells

7. HIV/AIDS  HIV = virus  Human Immunodeficiency Virus  AIDS = loss of immune system function  Acquired Immunodeficiency Syndrome

8. How?  HIV-infected cells eventually die after producing many viruses  HIV only infects cells that have protein CD4 on surface  CD4 cells = miscellaneous cells - helper T cells and macrophages essential components of immune system  HIV present in some blood and body fluids of infected people  Therefore:

9. How?  Without treatment: 1. immune system is disabled (AIDS) 2. Uncontrolled replication of HIV 3. Death from opportunistic infections

10. Why So Dangerous?  Kills immune system so you can’t fight it  Reverse transcriptase has high error rate – many mutations in HIV genome – constantly changing virus – hard to become immune to it or make vaccine  Infectious for long time – widespread epidemic

11. AIDS Treatments  Antibiotics for opportunistic infections (rifampin – inhibits RNApol of prokaryotes; no effect on eukaryotic RNApol; therefore kills bacteria, but no effect on HIV)  Anti-HIV drugs targeted to parts of HIV that are not present or needed in normal human cells (therefore kill virus, but not host)  “Coctail” of many nucleoside analogs if mutation occurs  HIV protease – bind to active site and prevent enzyme from working, therefore virus doesn’t mature into active form, therefore can’t infect cells

12. AIDS Treatments  Reverse transcriptase, HIV protease, and immune system reduces levels of HIV significantly

13. Questions?