Lentiviral Vif degrades the APOBEC3Z3/APOBEC3H protein of its mammalian host and is capable of cross-species activity.
All lentiviruses except equine infectious anemia virus (EIAV) use the small accessory protein Vif to counteract the restriction activity of the relevant APOBEC3 (A3) proteins of their host species. Prior studies have suggested that the Vif-A3 interaction is species specific. Here, using the APOBEC3H (Z3)-type proteins from five distinct mammals, we report that this is generally not the case: some lentiviral Vif proteins are capable of triggering the degradation of both the A3Z3-type protein of their normal host species and those of several other mammals. For instance, SIV(mac) Vif can mediate the degradation of the human, macaque, and cow A3Z3-type proteins but not of the sheep or cat A3Z3-type proteins. Maedi-visna virus (MVV) Vif is similarly promiscuous, degrading not only sheep A3Z3 but also the A3Z3-type proteins of humans, macaques, cows, and cats. In contrast to the neutralization capacity of these Vif proteins, human immunodeficiency virus (HIV), bovine immunodeficiency virus (BIV), and feline immunodeficiency virus (FIV) Vif appear specific to the A3Z3-type protein of their hosts. We conclude, first, that the Vif-A3Z3 interaction can be promiscuous and, second, despite this tendency, that each lentiviral Vif protein is optimized to degrade the A3Z3 protein of its mammalian host. Our results thereby suggest that the Vif-A3Z3 interaction is relevant to lentivirus biology.
Department of Biochemistry, Molecular Biology and Biophysics, Institute for Molecular Virology, Center for Genome Engineering,and Comparative and Molecular Biology Graduate Program, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Rebecca S
RS
Larue
Joy
J
Lengyel
Stefán R
SR
Jónsson
Valgerdur
V
Andrésdóttir
Reuben S
RS
Harris
D000818:Animals; D002415:Cats; D002417:Cattle; D043525:Cytosine Deaminase / Q000037:antagonists & inhibitors*; D016346:Gene Products, vif / Q000378:metabolism*; D006801:Humans; D016086:Lentivirus / Q000472:pathogenicity*; D008251:Macaca; D012756:Sheep; D037521:Virulence Factors / Q000378:metabolism*
D016346:Gene Products, vif; D037521:Virulence Factors; D043525:Cytosine Deaminase