Structural Adaptability in HIV-2 Vif Drives Broad Antagonism of APOBEC3G

Authors

Ronayne, E. K., Lilly, M., Lin, X., Niu, Y., Chesarino, N. M., Emerman, M., Cheng, Y., Gross, J. D.

Abstract

APOBEC3G (A3G), a restriction factor, is a barrier for zoonosis and targeted for degradation by the lentiviral protein Vif. Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 arose from transmissions of lentiviruses from Old World monkeys to hominid primates. While HIV-1 Vif needed to adapt to specific residues in the arms race interface with A3G, HIV-2 Vif has greater tolerance for diversity there. Here, our cryo-EM structure of HIV-2 Vif and human A3G allows us to explore the mechanism underlying HIV-2 Vif broad specificity. While HIV-2 Vif does bind the arms race interface on A3G, HIV-2 Vif encodes tryptophans with low backbone stability to engage another interface on A3G. We propose a model where flexible loops in HIV-2 Vif undergo conformational selection to recognize diverse A3Gs, whereas the equivalent loops in HIV-1 Vif are preorganized to bind hA3G.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 24 Sep 2026.

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