In vivo evolution of env in SHIV-AD8_EO-infected rhesus macaques after AAV-vectored delivery of eCD4-Ig.

ABSTRACT: eCD4-immunoglobulin (Ig) is an HIV entry inhibitor that mimics the engagement of both CD4 and CCR5 with the HIV envelope (Env) protein, a property that imbues it with remarkable potency and breadth. However, env is exceptionally genetically malleable and can evolve to escape a wide variety of entry inhibitors. Here we document the evolution of partial eCD4-Ig resistance in SHIV-AD8_EO-infected rhesus macaques (RMs) treated with adeno-associated virus vectors encoding eCD4-Ig. In one RM, setpoint viremia plateaued at 1,000 vRNA copies/mL, despite concomitant serum concentrations of eCD4-Ig in the 60-110 μg/mL range, implying that the virus had gained partial eCD4-Ig resistance. Env mutations occurring prominently in this animal were cloned and further characterized. Three of these

SUBMITTER: O'Hagan D 

PROVIDER: S-EPMC11853013 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature