History says, don’t hope On this side of the grave But then, once in a lifetime
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Transcript of History says, don’t hope On this side of the grave But then, once in a lifetime
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History says, don’t hopeOn this side of the graveBut then, once in a lifetimeThe longed-for tidal waveOf justice can rise upAnd hope and history rhyme.
Seamus Heaney,1995 Nobel Laureate in Literature1996 UNC commencement speaker “Voices from Lemnos”
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http://www.avert.org/his81_86.htm
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 andThe FDA licenses the first blood test for AIDS
The dawn of HIVA retrovirus causes AIDS
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http://www.avert.org/his81_86.htm
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 andThe FDA licenses the first blood test for AIDS
But what isa retrovirus?
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http://www.avert.org/his81_86.htm
But what isa retrovirus?
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THE BIOLOGY OF HIV, SIV, AND OTHER LENTIVIRUSES: Harrington and Swanstrom
Retroviruses are part of a big family tree!
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http://www.avert.org/his81_86.htm
To understand this discoveryWe need to go back to the beginning
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DNA -> RNA -> Proteins
The central dogma--Don’t forget this!
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We called this step translation
DNA -> RNA -> Proteins
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How about this step?
DNA -> RNA -> Proteins
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It’s called Transcription
DNA -> RNA -> Proteins
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users.ugent.be/.../principles/centraldogma.html
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• 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).
As a general rule, one gene encodes one protein
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This information flows requiresmachinery to carry it out
DNA RNA Protein
ReplicationDNA Polymerase
Transcription Translation
RNA Polymerase Ribosome
Process in Black, Enzyme in Blue
Enzymes are machines (most often made of only proteins) that catalyze a specific biochemical reaction
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Transcription looks like this
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Or in a slightly more detailed view
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Many viruses have genomes like ours, composed of DNA
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Other viruses have genomes that skip DNA
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But retroviruses do things differently
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Retroviruses. CSHL Press Fig. 1-5
RNA
DNA
RNA
But retroviruses do things differently
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Retroviruses. CSHL Press Fig. 1-5
RNA
DNA
RNA
This part is BACKWARDS
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Retroviruses. CSHL Press Fig. 1-5
RNA
DNA
RNA
How do they do that??
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Let’s take a closer look at the virus
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Let’s take a closer look at the virus
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How does HIV infect new people?
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How does HIV infect new people?
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How does HIV infect new people?
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How does HIV infect new people?
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Now let’s look closely to what happens when virus enters T cells
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And if we look Even more closely
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Retroviruses have stripped down genomesSo they make good use of what they have
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Let’s look at reverse transcriptase
Science. 1992 Jun 26;256(5065):1783-90
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It’s a distant relative of DNA polymerase!
=Bacterial DNA polymersae
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Encoded in pol are reverse transcriptase, RNAse H, and integrase!
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Reverse transcriptase, the amazing enzyme that does it all
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This will be important later!
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This remarkable reversal of the central dogma wasSimultaneously discovered by David Baltimore and Howard TeminAnd earned them the1975 Nobel Prize in Medicine or Physiology
David Baltimore
Howard Temin
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Now that the provirus is integrated in your DNA,It can generate new viruses
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This involves transcription,Translation and processing of viral proteins
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The Gag protein gets cleaved into piecesby an enzyme called a protease
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The Gag protein gets cleaved into piecesby an enzyme called a protease
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Gag Capsid
Matrix
This cleavage is essential to make an infectious virion!
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