3.1. aids - AIDS and antiretrovirals Human Immunodeficiency...

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AIDS and antiretrovirals
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Human Immunodeficiency Virus (HIV) Lipid enveloped Retrovirus — two copies of viral RNA genome 11.7 million deaths — WHO 5.8 million in 1997 alone infected and 30.6 million living with infection Infection of CD4 T cells and destruction with half-life of two days
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Fifteen Proteins and RNA 4 structural proteins (gag): MA (Matrix), CA (Capsid), NC (Nucleocapsid), p6 2 envelope proteins (env): SU (gp120), TM (gp41) 3 enzymes (gag-pol): PR (Protease), RT (Reverse Transcriptase), IN (Integrase) 6 accessory proteins: Vpr, Vif, Vpu, Tat, Rev, Nef
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Highly Active Antiretroviral Therapy (HAART)
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As of June 2002
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Fifteen Proteins and RNA 4 structural proteins (gag): MA (Matrix), CA (Capsid), NC (Nucleocapsid), p6 2 envelope proteins (env): SU (gp120), TM (gp41) 3 enzymes (gag-pol): PR (Protease), RT (Reverse Transcriptase), IN (Integrase) 6 accessory proteins: Vpr, Vif, Vpu, Tat, Rev, Nef
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Infection of CD4 + T cells Reverse Transcription
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RT RT RT tRNA 3 Lys
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Pol I Pol α RT Pol β Polymerases are highly conserved
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Fingers Thumb Palm 5’ template 3’ primer Position duplex DNA Interact with Incoming dNTP and template base Catalytic Domain
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RT has no editing site Mutations 10 9 new cells infected per day in latent HIV-infected patients Point mutations generated 10 4 -10 5 times per day
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Reverse Transcriptase Dimer p66-p51 p51 is proteolytically processed and inactive form of p66
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Fingers Palm Connection Thumb Catalytic Site of p51 destroyed by altered conformation of connection domain
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p66-p51 p51 interacts with RNase H domain of p66 p51 important for overall structure of p66
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