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CARD8 is an inflammasome sensor for HIV-1 protease activity.

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.

SUBMITTER: Wang Q

PROVIDER: S-EPMC8029496 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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CARD8 is an inflammasome sensor for HIV-1 protease activity.

Wang Qiankun Q Gao Hongbo H Clark Kolin M KM Mugisha Christian Shema CS Davis Keanu K Tang Jack P JP Harlan Gray H GH DeSelm Carl J CJ Presti Rachel M RM Kutluay Sebla B SB Shan Liang L

Science (New York, N.Y.) 20210204 6535

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. Pr ...[more]

PMID: 33542150

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