CARD8 is an inflammasome sensor for HIV-1 protease activity

Qiankun Wang, Hongbo Gao, Kolin M. Clark, Christian Shema Mugisha, Keanu Davis, Jack P. Tang, Gray H. Harlan, Carl J. DeSelm, Rachel M. Presti, Sebla B. Kutluay, Liang Shan

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

HIV-1 has high mutation rates and exists as mutant swarms within the host. Rapid evolution of HIV-1 allows the virus to outpace the host immune system, leading to viral persistence. Approaches to targeting immutable components are needed to clear HIV-1 infection. Here, we report that the caspase recruitment domain-containing protein 8 (CARD8) inflammasome senses HIV-1 protease activity. HIV-1 can evade CARD8 sensing because its protease remains inactive in infected cells before viral budding. Premature intracellular activation of the viral protease triggered CARD8 inflammasome-mediated pyroptosis of HIV-1-infected cells. This strategy led to the clearance of latent HIV-1 in patient CD4+T cells after viral reactivation. Thus, our study identifies CARD8 as an inflammasome sensor of HIV-1, which holds promise as a strategy for the clearance of persistent HIV-1 infection.

Original languageEnglish
Article number1224
JournalScience
Volume371
Issue number6535
DOIs
StatePublished - Mar 19 2021

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