A human-specific motif facilitates CARD8 inflammasome activation after HIV-1 infection.

ABSTRACT: Inflammasomes are cytosolic innate immune complexes that assemble upon detection of diverse pathogen-associated cues and play a critical role in host defense and inflammatory pathogenesis. Here, we find that the human inflammasome-forming sensor CARD8 senses HIV-1 infection via site-specific cleavage of the CARD8 N-terminus by the HIV protease (HIV-1^PR). HIV-1^PR cleavage of CARD8 induces pyroptotic cell death and the release of pro-inflammatory cytokines from infected cells, processes regulated by Toll-like receptor stimulation prior to viral infection. In acutely infected cells, CARD8 senses the activity of both de novo translated HIV-1^PR and packaged HIV-1^PR that is released from the incoming virion. Moreover, our evolutionary analyses reveal t

SUBMITTER: Kulsuptrakul J 

PROVIDER: S-EPMC10359095 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature