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

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

Author information

1
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Divisions of Human Biology and Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
3
Divisions of Human Biology and Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: memerman@fredhutch.org.
4
Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: jdgross@cgl.ucsf.edu.

Abstract

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

PMID:
31830442
PMCID:
PMC6913891
[Available on 2020-12-11]
DOI:
10.1016/j.chom.2019.10.014

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