Evasion of CARD8 Activation During HIV-1 Assembly.

ABSTRACT: As intracellular parasites, viruses must devise sophisticated mechanisms to produce and assemble viral components while suppressing activation of innate immune effectors. Here, we report that coordination of HIV-1 assembly by the viral polyprotein Gag suppresses inappropriately-timed protease (PR) activity to evade the PR activity sensor, CARD8. Employing mutants of Gag, we show that disruption of domains controlling viral assembly site (MA) or virus particle release (NC and p6) lead to premature activation of PR and the CARD8 inflammasome, resulting in IL-1β secretion and pyroptotic cell death. Further, we demonstrate that previously-observed host-adaptive mutations in HIV-1 MA (M30K) and p6 (PTAP duplication) associated with greater fitness in humans differentially modulate the process o

SUBMITTER: Hughes IK 

PROVIDER: S-EPMC12139941 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature