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Western University
Biology 1001A
Tom Haffie

Biology1001 Evolution in Action: Human Immunodeficiency Virus September 12, 2012  Viruses aren’t on the tree of life because they aren’t living organisms.  Not considered to be alive because they aren’t cellular in themselves, they need to infiltrate a host cell in order to persist  Viruses are obligate cellular parasites (needs host cell -> uses machinery of the host cell to make many copies of the virus)  Anti-viral therapy often has serious side effects  This is because the virus uses many important infrastructure of the cells, so it’s difficult to find a drug that will kill the virus because it would do a lot of collateral damage and take out the host cells as well  HIV is a retrovirus:  Usually: DNA -> RNA -> proten (central dogma of molecular biology)  Retroviruses work around this rule: HIV & retroviruses store their information in the form of RNA rather than DNA  Uses reverse transcription where RNA is used as a template to generate DNA (highly error- prone because it doesn’t have proofreading enzymes)  HIV only has 8 genes  Viral Lifecycle  Look at PPT slide:  Virion recognizes host cell and fuses onto the host cell membrane  Virion (viral particle) enters host cell  Reverse transcriptase -> viral DNA  Integrase splices viral DNA right into host DNA  Host cell takes over and acts as a stage that’s been hijacked  Viral DNA is transcribed, translated  New virions assemble and bud off or lyse out  Want to design Anti-retroviral therapies (ART) -> find which step is specific to HIV and try to make them dysfunctional  ARTs inhibit virus-specific enzymes  AZT mimics thymidine and inhibits reverse transcriptase  One of the first known treatments to HIV  AZT is a lot like DNA -> reverse transcriptase molecule grabs onto AZT instead of DNA, which stalls the process because reverse transcriptase cannot proceed; the chain is interrupted  However, it eventually stops working  (around 6 months)  What happened? Why did it stop working?  HIV evolved and found a way around the drug.  HIV mutation is very high, s
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