The CARD8 inflammasome dictates HIV/SIV pathogenesis and disease progression.

ABSTRACT: While CD4⁺ T cell depletion is key to disease progression in people living with HIV and SIV-infected macaques, the mechanisms underlying this depletion remain incompletely understood, with most cell death involving uninfected cells. In contrast, SIV infection of "natural" hosts such as sooty mangabeys does not cause CD4⁺ depletion and AIDS despite high-level viremia. Here, we report that the CARD8 inflammasome is activated immediately after HIV entry by the viral protease encapsulated in incoming virions. Sensing of HIV protease activity by CARD8 leads to rapid pyroptosis of quiescent cells without productive infection, while T cell activation abolishes CARD8 function and increases permissiveness to infection. In humanized mice reconstituted with CARD8-deficient cells

SUBMITTER: Wang Q 

PROVIDER: S-EPMC10919936 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature