6p59

Publication Abstract from PubMed

Primate lentiviruses encode a Vif protein that counteracts the host antiviral APOBEC3 (A3) family members. The adaptation of Vif to species-specific A3 determinants is a critical event that allowed the spillover of a lentivirus from monkey reservoirs to chimpanzees and subsequently to humans, which gave rise to HIV-1 and the acquired immune deficiency syndrome (AIDS) pandemic. How Vif-A3 protein interactions are remodeled during evolution is unclear. Here, we report a 2.94 A crystal structure of the Vif substrate receptor complex from simian immunodeficiency virus isolated from red-capped mangabey (SIVrcm). The structure of the SIVrcm Vif complex illuminates the stage of lentiviral Vif evolution that is immediately prior to entering hominid primates. Structure-function studies reveal the adaptations that allowed SIVrcm Vif to antagonize hominid A3G. These studies show a partitioning between an evolutionarily dynamic specificity determinant and a conserved protein interacting surface on Vif that enables adaptation while maintaining protein interactions required for potent A3 antagonism.

Structural Basis for a Species-Specific Determinant of an SIV Vif Protein toward Hominid APOBEC3G Antagonism.,Binning JM, Chesarino NM, Emerman M, Gross JD Cell Host Microbe. 2019 Dec 11;26(6):739-747.e4. doi: 10.1016/j.chom.2019.10.014. PMID:31830442^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.