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13th International HIV Drug Resistance Workshop8–12 June 2004, Tenerife Sur-Costa Adeje, Canary Islands, Spain |
The past 3 years has seen important advances in our understanding of the mechanisms of intracellular resistance to retroviral replication. The first resistance gene described was FV-1, a Gag-like cellular protein, that blocks the replication of murine leukaemia virus postentry. More recent studies on the Vif accessory protein of HIV led to the identification of the cellular cytidine deaminase APOBEC3G as a potent innate inhibitor of HIV replication. In HIV that is deleted for Vif (Δvif), APOBEC3G is encapsidated into the virions during virus assembly. When the virus infects new target cells and initiates reverse transcription, the encapsidated enzyme attacks the minus-strand of the reverse transcripts, modifying cytosines to uracil and resulting in G→A hypermutation on the subsequently synthesized plus-strands. APOBEC3G-induced G→A mutation has molded the HIV-1 genome over evolution resulting in an enrichment for A nucleotides. In cells infected with wild-type virus Vif induces the degradation of APOBEC3G, preserving the integrity of the viral genome. Most recently, studies aimed at understanding the resistance of primate cells to HIV-1 led to the identification of Trim5-alpha. Primate, but not human Trim5-alpha blocks HIV infection at reverse transcription by a mechanism that is not yet known. Current understanding of these host factors will be discussed with an emphasis on APOBEC3G.
Presenting author: NR Landau
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2004-06-08
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