The CARD8 inflammasome dictates HIV/SIV pathogenesis and disease progression.
Cell
; 187(5): 1223-1237.e16, 2024 Feb 29.
Article
de En
| MEDLINE
| ID: mdl-38428396
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, CD4+ depletion is delayed despite high viremia. Finally, we discovered loss-of-function mutations in CARD8 from "natural hosts," which may explain the peculiarly non-pathogenic nature of these infections. Our study suggests that CARD8 drives CD4+ T cell depletion during pathogenic HIV/SIV infections.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Infections à VIH
/
Syndrome d'immunodéficience acquise du singe
/
Inflammasomes
Limites:
Animals
/
Humans
Langue:
En
Journal:
Cell
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique