Revealing the Association of cynomolgus monkey APOBEC3F with Their Anti-HIV-1 Activity Using Cell-Based Assay for the Development of HIV-1 Animal Model

Abstract

HIV-1 (Human Immunodeficiency Virus type 1) is a retrovirus that primarily infects CD4+ T lymphocytes, crucial components of the immune system. Currently, there is no definitive cure that can eliminate all forms of the virus, including latent reservoirs. This ongoing challenge is partly attributed to the absence of suitable animal models that accurately mimic HIV-1 pathogenesis, hindering the development of effective treatments. To tackle this issue, the project aims to establish a cynomolgus monkey model to enhance targeted research for an HIV-1 cure and to investigate various apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3/A3) proteins within this context. The research will utilize single-cycle assays to assess the antiviral activity of cynomolgus monkey (cm) A3F protein in human embryonic kidney (HEK) 293T cells against both vesicular stomatitis virus G protein (VSV-G) pseudotyped HIV-1 and monkey-tropic HIV-1 (HIV-1mt) with Vif simian immunodeficiency virus of macaques (SIVmac), followed by evaluations of viral infectivity. Control experiments with wild-type (WT) cmA3F protein have shown results consistent with previous studies, indicating readiness to test cmA3F mutants. The mutations analyzed include V237I, 967X, and S246T/R247H, each displaying distinct effects on viral infectivity. Notably, the V237I mutation exhibited stronger inhibition than WT cmA3F, while the 967X mutation surprisingly demonstrated higher inhibitory effects despite predictions of premature termination. The S246T/R247H mutation yielded inconsistent results. Given the novelty of these mutations and limited testing, further evaluation is crucial for a comprehensive understanding of their functional roles.