The biggest challenge to immune control of HIV infection is the rapid within-host viral evolution, which allows selection of viral variants that escape from T cell and antibody recognition. Thus, it is impossible to clear HIV infection without targeting “immutable” components of the virus. Unlike the adaptive immune system that recognizes cognate epitopes, the CARD8 inflammasome senses the essential enzymatic activity of the HIV-1 protease, which is immutable for the virus. Hence, all subtypes of HIV clinical isolates can be recognized by CARD8. In HIV-infected cells, the viral protease is expressed as a subunit of the viral Gag-Pol polyprotein and remains functionally inactive prior to viral budding. A class of anti-HIV drugs, the non-nucleoside reverse transcriptase inhibitors (NNRTIs), can promote Gag-pol dimerization and subsequent premature intracellular activation of the viral protease. NNRTI treatment triggers CARD8 inflammasome activation, which leads to pyroptosis of HIV-infected CD4+ T cells and macrophages. Targeting the CARD8 inflammasome can be a potent and broadly effective strategy for HIV eradication.

Original languageEnglish
Title of host publicationAdvances in Immunology
EditorsFrederick W. Alt, Kenneth M. Murphy
PublisherAcademic Press Inc.
Number of pages42
ISBN (Print)9780443193286
StatePublished - Jan 2023

Publication series

NameAdvances in Immunology
ISSN (Print)0065-2776
ISSN (Electronic)1557-8445


  • CD4+ T-cell
  • Caspase
  • HIV
  • Inflammasome
  • Protease


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