Year: 2026
Type: preprint
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's 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.
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Howard Hughes Medical Institute, Houston Advanced Research Center, National Institutes of Health, Center for AIDS Research, University of Washington, University of California, San Francisco, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
Awards: G1255407591, G1557483336, G3181090803, G328662883, G5134280556, Graduate Research Fellowship Program (GRFP), G7383342067, G8783302961, G8917620550, Advancing cryo-EM technology to address difficult biological questions, HARC: HIV accessory and regulatory complexes, UCSF-Bay Area Center for AIDS Research
OpenAlex ID: W7214232401