CARD8 Inflammasome Activation by HIV-1 Protease

Kolin M Clark; Qiankun Wang; Liang Shan

doi:10.1007/978-1-0716-3040-2_6

CARD8 Inflammasome Activation by HIV-1 Protease

Methods Mol Biol. 2023:2641:67-79. doi: 10.1007/978-1-0716-3040-2_6.

Authors

Kolin M Clark¹, Qiankun Wang¹, Liang Shan^{2

3}

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
² Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. liang.shan@wustl.edu.
³ Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO, USA. liang.shan@wustl.edu.

PMID: 37074642
DOI: 10.1007/978-1-0716-3040-2_6

Abstract

The pattern recognition receptor CARD8 is an inflammasome sensor for intracellular HIV-1 protease activity. Previously, the only method for studying the CARD8 inflammasome has been through utilizing DPP8/DPP9 inhibitors including Val-boroPro (VbP) to modestly and nonspecifically activate the CARD8 inflammasome. The identification of HIV-1 protease as a target for sensing by CARD8 has opened the door for a new method of studying the underlying mechanism of CARD8 inflammasome activation. Additionally, triggering the CARD8 inflammasome offers a promising strategy for reducing HIV-1 latent reservoirs. Here we describe the methods to study CARD8 sensing of HIV-1 protease activity through non-nucleoside reverse transcriptase inhibitor (NNRTI)-mediated pyroptosis of HIV-1-infected immune cells and through an HIV and CARD8 co-transfection model.

Keywords: CARD8 inflammasome; Caspase-1 (CASP1); HIV-1; Protease; Pyroptosis.

MeSH terms

Apoptosis Regulatory Proteins / metabolism
CARD Signaling Adaptor Proteins* / metabolism
HIV Protease
Inflammasomes* / metabolism

Substances

Inflammasomes
CARD Signaling Adaptor Proteins
p16 protease, Human immunodeficiency virus 1
Apoptosis Regulatory Proteins
HIV Protease