Related Experiment Video

Updated: May 7, 2026

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

21.2K

CARD8 is an inflammasome sensor for HIV-1 protease activity

Qiankun Wang1, Hongbo Gao1, Kolin M Clark1

  • 1Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.

Science (New York, N.Y.)
|February 5, 2021
PubMed

Insights

The CARD8 inflammasome detects HIV-1 protease activity. Activating this pathway clears persistent HIV-1 infection by triggering pyroptosis in infected cells.

Area of Science:

  • Immunology
  • Virology
  • Cellular Biology

Background:

  • Human Immunodeficiency Virus type 1 (HIV-1) exhibits high mutation rates, leading to rapid evolution and immune evasion.
  • Viral persistence, particularly latent HIV-1 reservoirs, poses a significant challenge for complete eradication.
  • Targeting conserved viral components is crucial for developing effective HIV-1 clearance strategies.

Purpose of the Study:

  • To identify host factors that sense HIV-1 activity.
  • To investigate the role of the CARD8 inflammasome in detecting HIV-1 protease.
  • To explore the potential of targeting the CARD8 inflammasome for clearing persistent HIV-1 infection.

Main Methods:

  • Assessed CARD8 inflammasome activation in response to HIV-1 protease activity.
  • Investigated mechanisms of HIV-1 evasion of CARD8 sensing.
  • Induced premature intracellular activation of HIV-1 protease.
  • Evaluated the clearance of latent HIV-1 in patient CD4+ T cells.

Main Results:

  • The CARD8 inflammasome was identified as a sensor of HIV-1 protease activity.
  • HIV-1 evades CARD8 sensing through protease inactivity before viral budding.
  • Premature protease activation induced CARD8 inflammasome-mediated pyroptosis, clearing infected cells.
  • Latent HIV-1 was cleared in patient CD4+ T cells upon viral reactivation and CARD8 activation.

Conclusions:

  • CARD8 acts as a critical inflammasome sensor for HIV-1 protease.
  • Targeting the CARD8 inflammasome pathway offers a novel strategy for eliminating persistent HIV-1 reservoirs.
  • This approach holds promise for achieving a functional cure for HIV-1 infection.

More Related Videos

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages06:52

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages

Published on: May 21, 2018

11.0K
Single-Cell Characterization of Calcium Influx and HIV-1 Infection using a Multiparameter Optofluidic Platform07:15

Single-Cell Characterization of Calcium Influx and HIV-1 Infection using a Multiparameter Optofluidic Platform

Published on: May 18, 2021

3.4K

Related Concept Videos

Retroviruses02:33

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
Enzyme-Linked Immunosorbent Assay01:33

Enzyme-Linked Immunosorbent Assay

In 1971, Peter Perlman and Eva Engvall developed an Enzyme-linked immunosorbent assay (ELISA or EIA). ELISA differs from western blot in that the assays are conducted in microtiter plates or in vivo rather than on an absorbent membrane.
There are many different types of ELISAs, but they all involve an antibody molecule whose constant region binds an enzyme, leaving the variable region free to bind its specific antigen.  Enzyme-substrate reaction allows the antigen to be visualized or quantified.
Immunodeficiency Diseases01:25

Immunodeficiency Diseases

Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency disorders...
Cytomegalovirus Disease01:27

Cytomegalovirus Disease

Cytomegalovirus (CMV) disease is caused by human cytomegalovirus, a double-stranded DNA virus of the Herpesviridae family. While primary CMV infection is often asymptomatic in immunocompetent individuals, the virus can cause severe disease in neonates and immunocompromised patients. CMV is the most common cause of congenital viral infection in the United States, and a major pathogen in solid organ and hematopoietic stem cell transplant recipients.CMV is transmitted via bodily fluids, sexual...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...