CARD8 is an inflammasome sensor for HIV-1 protease activity.
| Publication Type | Academic Article |
| Authors | Wang Q, Gao H, Clark K, Mugisha C, Davis K, Tang J, Harlan G, DeSelm C, Presti R, Kutluay S, Shan L |
| Journal | Science |
| Volume | 371 |
| Issue | 6535 |
| Date Published | 02/04/2021 |
| ISSN | 1095-9203 |
| Keywords | CARD Signaling Adaptor Proteins, HIV Infections, HIV Protease, HIV-1, Inflammasomes, Neoplasm Proteins, Pyroptosis |
| 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. |
| DOI | 10.1126/science.abe1707 |
| PubMed ID | 33542150 |
| PubMed Central ID | PMC8029496 |