Federal Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded The Regents of the University of California, San Francisco a $809,975 Project Grant under the Allergy and Infectious Diseases Research program (CFDA 93.855) on July 7, 2026, with a completion date of June 30, 2031. This five-year research project investigates the evolutionary mechanisms underlying broad APOBEC3 (A3) neutralization by primate lentiviral VIF (Viraemia Inducing Factor) proteins, with particular focus on understanding how HIV-2 VIF broadly antagonizes human A3 family members without requiring adaptive mutations. The research employs cryo-electron microscopy (cryo-EM), biochemical studies, and virological approaches to characterize protein interaction surfaces, specifically examining a tryptophan-rich motif (WXWW) in HIV-2 VIF loop 3 that interacts with antivirally-active human A3H haplotype II and A3G.

The project directly addresses a critical gap in understanding molecular mechanisms of viral adaptation and cross-species transmission of lentiviruses, which has direct relevance to HIV pandemic origins and ongoing therapeutic development. Deliverables include refined structural characterizations of HIV-2 VIF in complex with human A3G, comparative modeling studies between SIVSMM (Simian Immunodeficiency Virus, Sooty Mangabey) VIF and sooty mangabey A3G, and mechanistic insights into residue polymorphism tolerance in HIV-2 VIF loop 5. This basic science research contributes to the broader NIAID mission of supporting investigator-initiated biomedical research on infectious diseases and immunology conducted at academic medical research institutions.