SIV-specific neutralizing antibody induction following selection of a PI3K drive-attenuated <i>nef</i> variant.

ABSTRACT: HIV and simian immunodeficiency virus (SIV) infections are known for impaired neutralizing antibody (NAb) responses. While sequential virus-host B cell interaction appears to be basally required for NAb induction, driver molecular signatures predisposing to NAb induction still remain largely unknown. Here we describe SIV-specific NAb induction following a virus-host interplay decreasing aberrant viral drive of phosphoinositide 3-kinase (PI3K). Screening of seventy difficult-to-neutralize SIV_mac239-infected macaques found nine NAb-inducing animals, with seven selecting for a specific CD8⁺ T-cell escape mutation in viral nef before NAb induction. This Nef-G63E mutation reduced excess Nef interaction-mediated drive of B-cell maturation-limiting PI3K/mammalian targ

SUBMITTER: Yamamoto H 

PROVIDER: S-EPMC11875539 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature