History says, don’t hope On this side of the grave But then, once in a lifetime

1. History says, don’t hope On this side of the grave But then, once in a lifetime The longed-for tidal wave Of justice can rise up And hope and history rhyme. Seamus Heaney, 1995 Nobel Laureate in Literature 1996 UNC commencement speaker “Voices from Lemnos”

2. “Crime once exposed has no refuge but in audacity” “To ravage, to slaughter, to usurp under false titles, they call empire; and where they make a desert, they call it peace” Publius Cornelius Tacitus (56-117 CE)

3. The dawn of HIV A retrovirus causes AIDS In May 1983: doctors at the Institute Pasteur in France reported that they had isolated a new virus, which they suggested might be the cause of AIDS. Barre-Sinoussi F. … and Montagnier L. (1983), 'Isolation of a T-Lymphotropic retrovirus from a patient at risk for Acquired Immune Deficiency Syndrome (AIDS)', Science, May 20 In May 1983: doctors at the NIH in the US reported that a retrovirus virus related to Human T cell Leukemia virus was present in patients with AIDS. Gelman EP … and Gallo RC. (1983), “Proviral DNA of a retrovirus, human T-cell leukemia virus, in two patients with’AIDS, Science, May 20 January 1985 It becomes clear that LAV and HTLV-III are the same virus and The FDA licenses the first blood test for AIDS http://www.avert.org/his81_86.htm

4. But what is a retrovirus? In May 1983: doctors at the Institute Pasteur in France reported that they had isolated a new virus, which they suggested might be the cause of AIDS. Barre-Sinoussi F. … and Montagnier L. (1983), 'Isolation of a T-Lymphotropic retrovirus from a patient at risk for Acquired Immune Deficiency Syndrome (AIDS)', Science, May 20 In May 1983: doctors at the NIH in the US reported that a retrovirus virus related to Human T cell Leukemia virus was present in patients with AIDS. Gelman EP … and Gallo RC. (1983), “Proviral DNA of a retrovirus, human T-cell leukemia virus, in two patients with’AIDS, Science, May 20 January 1985 It becomes clear that LAV and HTLV-III are the same virus and The FDA licenses the first blood test for AIDS http://www.avert.org/his81_86.htm

5. But what is a retrovirus? http://www.avert.org/his81_86.htm

6. To understand this discovery We need to go back to the beginning http://www.avert.org/his81_86.htm

7. The central dogma-- Did you forget this since the exam?

8. The central dogma-- Did you forget this since the exam? DNA -> RNA -> Proteins

9. We called this step translation DNA -> RNA -> Proteins

10. How about this step? DNA -> RNA -> Proteins

11. It’s called Transcription DNA -> RNA -> Proteins

13. As a general rule, one gene encodes one protein • Cellular machinery is largely made up of proteins. • Proteins are made up of chains or sequences of amino acids. • The sequence of these amino acids are "encoded" in the cell's DNA. DNA is transcribed into RNA, which is then translated into protein. • When one gene is mutated, one protein (a machine) is affected (usually disabled).

14. This information flows requires Machinery to carry it out DNA RNA Protein Transcription Translation RNA Polymerase Ribosome Replication DNA Polymerase Process in Black, Enzyme in BlueEnzymes are proteins that catalyze a specific biochemical reaction

15. Transcription looks like this

16. Or in a slightly more detailed view

17. Many viruses have genomes like ours, composed of DNA

18. Other viruses have genomes that skip DNA

19. But retroviruses do things differently

20. But retroviruses do things differently RNA DNA RNA Retroviruses. CSHL Press Fig. 1-5

21. This part is BACKWARDS RNA DNA RNA Retroviruses. CSHL Press Fig. 1-5

22. How do they do that?? RNA DNA RNA Retroviruses. CSHL Press Fig. 1-5

23. Let’s take a closer look at the virus

24. Let’s take a closer look at the virus

25. How does HIV infect new people?

26. How does HIV infect new people?

27. How does HIV infect new people?

28. How does HIV infect new people?

29. Now let’s look closely to what happens when virus enters T cells

31. And if we look Even more closely

32. And Even more closely

33. Retroviruses have stripped down genomes So they make good use of what they have

34. Retroviruses have stripped down genomes So they make good use of what they have

35. Retroviruses have stripped down genomes So they make good use of what they have

36. Let’s look at reverse transcriptase Science. 1992 Jun 26;256(5065):1783-90

37. It’s a distant relative of DNA polymerase!

38. Encoded in pol are reverse transcriptase, RNAse H, and integrase!

39. Reverse transcriptase, the amazing enzyme that does it all

40. This will be important later!

41. This remarkable reversal of the central dogma was Simultaneously discovered by David Baltimore and Howard Temin And earned them the 1975 Nobel Prize in Medicine or Physiology David Baltimore Howard Temin

42. Now that the provirus is integrated in your DNA, It can generate new viruses

43. This involves transcription, Translation and processing of viral proteins

44. The Gag protein gets cleaved into pieces by an enzyme called a protease

45. The Gag protein gets cleaved into pieces by an enzyme called a protease

46. The Gag protein gets cleaved into pieces by an enzyme called a protease Matrix Capsid Gag