Related Experiment Video

Updated: Aug 14, 2026

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

A poxvirus-encoded pyrin domain protein interacts with ASC-1 to inhibit host inflammatory and apoptotic responses to

James B Johnston1, John W Barrett, Steven H Nazarian

  • 1BioTherapeutics Research Group, Robarts Research Institute, 1400 Western Road, London, Ontario N6G 2V4, Canada.

Immunity
|December 17, 2005
PubMed

Insights

Poxviruses encode a protein that inhibits inflammasome activation, crucial for innate immunity. This viral protein blocks caspase-1 activation, impacting cytokine production and host defense during infection.

Area of Science:

  • Innate immunity
  • Molecular biology
  • Virology

Background:

  • Proinflammatory caspases are key in innate immune responses to infection.
  • Inflammasome assembly, involving PYD-containing proteins, is required for caspase activation.
  • Poxviruses utilize immune evasion strategies to ensure viral replication.

Purpose of the Study:

  • To identify and characterize poxvirus-encoded proteins that modulate inflammasome function.
  • To investigate the mechanism by which poxviruses interfere with host antiviral responses.
  • To understand the role of inflammasome inhibition in viral pathogenesis.

Main Methods:

  • Identification and characterization of a poxvirus-encoded PYD-containing protein.
  • Assays to assess the interaction with ASC-1 and inhibition of caspase-1 activation.
  • Generation and analysis of knockout viruses in host cells and animal models.

Main Results:

  • A poxvirus-encoded PYD protein was identified that interacts with ASC-1.
  • This viral protein inhibits caspase-1 activation and subsequent processing of IL-1beta and IL-18.
  • Knockout viruses lacking this protein exhibit impaired replication in immune cells and reduced virulence in vivo.

Conclusions:

  • Poxviruses employ a PYD-containing protein to inhibit inflammasome-mediated immunity.
  • Modulation of inflammasome function is a critical viral strategy for immune evasion.
  • Targeting the inflammasome allows poxviruses to circumvent host antiviral defenses and promote 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

Identifying Caspases and their Motifs that Cleave Proteins During Influenza A Virus Infection08:16

Identifying Caspases and their Motifs that Cleave Proteins During Influenza A Virus Infection

Published on: July 21, 2022

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
The Antiviral System of Bacteria and Archaea: CRISPR01:23

The Antiviral System of Bacteria and Archaea: CRISPR

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats is a adaptive immune system found in bacteria and archaea that protects against viral infections. This system enables prokaryotic cells to identify, remember, and neutralize foreign genetic elements, primarily bacteriophages, by storing fragments of the invader’s DNA as a genetic memory.The CRISPR immune response begins during an initial infection. Cas (CRISPR-associated) proteins play a central role in this defense.
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.