CARD8 is an inflammasome sensor for HIV-1 protease activity
Qiankun Wang, Hongbo Gao, Kolin M. Clark, Christian Shema Mugisha, Keanu Davis, Jack Pengfei Tang, Gray H. Harlan, Carl J. DeSelm, Rachel M. Presti, Sebla B. Kutluay, Liang Shan
Abstract
Eradicating the last vestiges of HIV After treatment with antiretroviral therapy, HIV-1 wild-type and escape variants can persist in a latent form, especially within CD4 + T cells, hindering efforts to eradicate the virus. Q. Wang et al. found that human CARD8, a member of the caspase recruitment domain (CARD)–containing family of innate immune sensors, is activatable by direct proteolysis of its N-terminus by HIV-1 protease. This cleavage should result in the programmed cell death of infected cells, but HIV-1 protease remains inactive and undetected as a subunit of the unprocessed Gag-Pol polyprotein. However, when infected cells were treated with non-nucleoside reverse transcriptase inhibitors, intracellular Gag-Pol dimerization was enhanced, resulting in CARD8-mediated caspase activation and pyroptosis. Targeting this pathway may be a promising way to eliminate residual HIV-1 in patients. Science , this issue p. eabe1707