12th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 22-25, 2005

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 5

Michael H. Malim
King's Coll London, UK

Work from a number of groups in the past three years has demonstrated that the cellular polynucleotide cytidine deaminases APOBEC3G and APOBEC3F are potent inhibitors of HIV infection. As such, they constitute a new form of innate, host-mediated resistance to viral infection. In the absence of the viral Vif protein, these enzymes are encapsidated by budding virus particles and then transferred to target cells where they catalyse the excessive deamination of cytidine (C) to uridine (U) in first strand reverse transcripts (or cDNAs). This results in both guanosine (G) to adenosine (A) hypermutation of viral plus stranded cDNA and an overall diminution in the accumulation of viral cDNAs. Together, these effects contribute to the very low infectivity of viruses produced in the absence of Vif, but in the presence of APOBEC3G/F. Vif protects HIV from these enzymes through the recruitment of cellular ubiquitin ligases, which then trigger their elimination by the proteasome. One current view of the opposing activities of Vif and the APOBEC3G/F proteins during natural infection is that they are in "equilibrium" with each other. Accordingly, increases in APOBEC protein function or levels, or interference with Vif function, could culminate in increases in mutation rates that could either confer selective advantages upon viral populations or, at more extreme levels, result in losses to virus infectivity and/or increases in G-to-A hypermutation. Sequencing of viruses during natural infection indicates that the latter can indeed occur, thus suggesting that perturbation of Vif/APOBEC function deserves consideration as a future therapeutic strategy.

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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.