Controlling lentiviruses: Single amino acid changes can determine specificity
- Shari M. Kaiser*,† and
- Michael Emerman†,‡
- *Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195; and†Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
The human immunodeficiency virus (HIV) is a member of the lentivirus family of retroviruses that we share with other primates. The known strains of primate lentiviruses fall into six major lineages identified from >25 species of African primates (1), and it is clear from phylogenetic analysis of lentiviral sequences that their evolutionary history involves a number of cross-species transmissions. Indeed, HIV-1 is a close relative of a virus found in chimpanzees (simian immunodeficiency virus from chimpanzees, or SIVcpz), and HIV-2 is a relative of a virus found in sooty mangabeys (SIVsmm). However, it is not clear whether other members of the primate lentivirus family could spread to humans under the right transmission conditions. Thus, it is important to understand the potential barriers that govern cross-species transmissions from animals to human. Two articles in this issue of PNAS (2, 3) and also an article in press at PNAS (4) indicate that a single amino acid position in a host antiviral enzyme called Apobec3G (5) may be one such barrier that protects humans from primate lentiviruses found in the widely distributed family of AGMs (Chlorocebus aethiops) (Fig. 1).
Host-specific interactions of Apobec3G with viral Vifs. Human Apobec3G encodes aspartate (D) at amino acid 128 and functionally interacts with HIV-1 Vif but not with SIVagm Vif, whereas AGM Apobec3G encodes a lysine (K) at amino acid 128 and functionally interacts with SIVagm Vif but not with HIV-1 Vif. The functional interactions can be reversed by mutating human Apobec3G to K at amino acid 128 and by mutating AGM Apobec3G to D at amino acid 128. Interactions are denoted by + or -. A positive interaction indicates that Apobec3G will be sensitive to Vif, and a negative interaction indicates that it will be resistant.
Innate cellular antiviral responses limit the damage that …
