SIV-specific neutralizing antibody induction following selection of a PI3K drive-attenuatednefvariant

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 21, 2023

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 NAb induction, driver molecular signatures predisposing induction still remain largely unknown. Here we describe SIV-specific following a interplay decreasing aberrant viral drive of phosphoinositide 3-kinase (PI3K). Screening seventy difficult-to-neutralize SIV mac239 -infected macaques found nine NAb-inducing animals, with seven selecting specific CD8 + T-cell escape mutation in nef before induction. This Nef-G63E reduced excess Nef interaction-mediated B-cell maturation-limiting PI3K/mammalian target rapamycin complex 2 (mTORC2). In vivo imaging cytometry depicted preferential perturbation cognate Envelope-specific cells, suggestive polarized contact-dependent transfer corroborating maturation post-mutant selection up Results collectively exemplify pattern extrinsically reciprocal human PI3K gain-of-function antibody-dysregulating disease, indicate that harnessing the PI3K/mTORC2 axis may facilitate against viruses including HIV/SIV.

Language: Английский

SIV-specific neutralizing antibody induction following selection of a PI3K drive-attenuated nef variant

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Aug. 8, 2023

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 NAb induction, driver molecular signatures predisposing induction still remain largely unknown. Here we describe SIV-specific following a interplay decreasing aberrant viral drive of phosphoinositide 3-kinase (PI3K). Screening seventy difficult-to-neutralize SIVmac239-infected macaques found nine NAb-inducing animals, with seven selecting specific CD8+ T-cell escape mutation in nef before induction. This Nef-G63E reduced excess Nef interaction-mediated B-cell maturation-limiting PI3K/mammalian target rapamycin complex 2 (mTORC2). In vivo imaging cytometry depicted preferential perturbation cognate Envelope-specific cells, suggestive polarized contact-dependent transfer corroborating maturation post-mutant selection up Results collectively exemplify pattern extrinsically reciprocal human PI3K gain-of-function antibody-dysregulating disease indicate that harnessing the PI3K/mTORC2 axis may facilitate against viruses including HIV/SIV.

Language: Английский