Structural Basis for a Species-Specific Determinant of an SIV Vif Protein toward Hominid APOBEC3G Antagonism

Cell Host Microbe. 2019 Dec 11;26(6):739-747.e4. doi: 10.1016/j.chom.2019.10.014.


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 Å 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.

Keywords: AIDS; APOBEC3; HIV; SIV; Vif; evolution; molecular arms race; restriction factors; ubiquitin proteasome pathway; viral accessory proteins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • APOBEC-3G Deaminase / metabolism
  • Acquired Immunodeficiency Syndrome
  • Animals
  • Cercocebus
  • Crystallography
  • Evolution, Molecular
  • Gene Products, vif* / chemistry
  • Gene Products, vif* / genetics
  • HIV-1 / genetics
  • HIV-1 / metabolism
  • Hominidae
  • Host-Pathogen Interactions
  • Humans
  • Lentivirus / genetics
  • Lentivirus / metabolism
  • Monkey Diseases / virology
  • Pan troglodytes
  • Primates
  • Simian Immunodeficiency Virus* / genetics
  • Simian Immunodeficiency Virus* / metabolism
  • vif Gene Products, Human Immunodeficiency Virus / chemistry
  • vif Gene Products, Human Immunodeficiency Virus / genetics
  • vif Gene Products, Human Immunodeficiency Virus / ultrastructure


  • Gene Products, vif
  • vif Gene Products, Human Immunodeficiency Virus
  • vif protein, Human immunodeficiency virus 1
  • vif protein, Human immunodeficiency virus 2
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human