2. Academic Validation
  3. CARD8 is an inflammasome sensor for HIV-1 protease activity

CARD8 is an inflammasome sensor for HIV-1 protease activity

  • Science. 2021 Mar 19;371(6535):eabe1707. doi: 10.1126/science.abe1707.
Qiankun Wang 1,  Hongbo Gao 1,  Kolin M Clark 1,  Christian Shema Mugisha 2,  Keanu Davis 2,  Jack P Tang 3,  Gray H Harlan 1,  Carl J DeSelm 3 4,  Rachel M Presti 1,  Sebla B Kutluay 2,  Liang Shan 5 4
Affiliations

Affiliations

  • 1 Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
  • 2 Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO, USA.
  • 3 Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO, USA.
  • 4 Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO, USA.
  • 5 Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. [email protected].
PMID: 33542150 DOI: 10.1126/science.abe1707
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.

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