Structural Adaptability in HIV-2 Vif Drives Broad Antagonism of APOBEC3G
- 1University of California, San Francisco
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.
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BibTeX
@misc{ronayne2026structural,
title = {{Structural Adaptability in HIV-2 Vif Drives Broad Antagonism of APOBEC3G}},
author = {E. K. Ronayne and M. Lilly and X. Lin and Y. Niu and N. M. Chesarino and M. Emerman and Y. Cheng and J. D. Gross},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.753272},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.753272v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Structural Adaptability in HIV-2 Vif Drives Broad Antagonism of APOBEC3G
AU - E. K. Ronayne
AU - M. Lilly
AU - X. Lin
AU - Y. Niu
AU - N. M. Chesarino
AU - M. Emerman
AU - Y. Cheng
AU - J. D. Gross
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.753272
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.753272v1
AB - 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.
ER -