title: The host restriction factor APOBEC3G and retroviral Vif protein coevolve due to ongoing genetic conflict.
abstract: APOBEC3G (A3G) is a host cytidine deaminase that inhibits retroviruses. HIV and related primate lentiviruses encode Vif, which counteracts A3G by inducing its degradation. This Vif-mediated A3G inhibition is species specific, suggesting that the A3G-Vif interaction has evolved as primate lentiviruses have adapted to their hosts. We examined the evolutionary dynamics of the A3G-Vif interaction within four African green monkey (AGM) subspecies, which are each naturally infected with a distinct simian immunodeficiency virus (SIV). We identified single amino acid changes within A3G in two AGM subspecies that render it resistant to Vif proteins, except for Vif from the viruses that naturally infect these subspecies. Moreover, experimental infection of AGMs shows that Vif can rapidly adapt to these arising Vif-resistant A3G genotypes. These data suggest that despite being generally nonpathogenic in its natural host, SIV infection selects for Vif-resistant forms of A3G in AGM populations, driving Vif counterevolution and functional divergence.
authors.affiliation: Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98195, USA.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Compton
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hirsch
authors.forename: Michael
authors.initials: M
authors.lastname: Emerman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D058070:Asymptomatic Diseases; D002522:Chlorocebus aethiops; D016000:Cluster Analysis; D003564:Cytidine Deaminase / Q000235:genetics*; D019143:Evolution, Molecular; D016346:Gene Products, vif / Q000235:genetics*; D005838:Genotype; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity
chemical_list: D016346:Gene Products, vif; D003564:Cytidine Deaminase