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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” 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 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 But what is a retrovirus? http://www.avert.org/his81_86.htm Retroviruses are part of a big family tree! THE BIOLOGY OF HIV, SIV, AND OTHER LENTIVIRUSES: Harrington and Swanstrom To understand this discovery We need to go back to the beginning http://www.avert.org/his81_86.htm The central dogma-Don’t forget this! DNA -> RNA -> Proteins We called this step translation DNA -> RNA -> Proteins How about this step? DNA -> RNA -> Proteins It’s called Transcription DNA -> RNA -> Proteins users.ugent.be/.../principles/centraldogma.html As a general rule, one gene encodes one protein • Cellular machines are largely made up of proteins. • Proteins are made up of chains 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). This information flows requires machinery to carry it out Transcription DNA RNA Polymerase Translation RNA Ribosome Protein Replication DNA Polymerase Process in Black, Enzyme in Blue Enzymes are machines (most often made of only proteins) that catalyze a specific biochemical reaction Transcription looks like this Or in a slightly more detailed view Many viruses have genomes like ours, composed of DNA Other viruses have genomes that skip DNA But retroviruses do things differently But retroviruses do things differently RNA DNA RNA Retroviruses. CSHL Press Fig. 1-5 This part is BACKWARDS RNA DNA RNA Retroviruses. CSHL Press Fig. 1-5 How do they do that?? RNA DNA RNA Retroviruses. CSHL Press Fig. 1-5 Let’s take a closer look at the virus Let’s take a closer look at the virus How does HIV infect new people? How does HIV infect new people? How does HIV infect new people? How does HIV infect new people? Now let’s look closely to what happens when virus enters T cells And if we look Even more closely Retroviruses have stripped down genomes So they make good use of what they have Let’s look at reverse transcriptase Science. 1992 Jun 26;256(5065):1783-90 It’s a distant relative of DNA polymerase! =Bacterial DNA polymersae Encoded in pol are reverse transcriptase, RNAse H, and integrase! Reverse transcriptase, the amazing enzyme that does it all This will be important later! 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 Now that the provirus is integrated in your DNA, It can generate new viruses This involves transcription, Translation and processing of viral proteins The Gag protein gets cleaved into pieces by an enzyme called a protease The Gag protein gets cleaved into pieces by an enzyme called a protease This cleavage is essential to make an infectious virion! Gag Matrix Capsid