Related Experiment Video

Updated: Sep 30, 2026

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry
05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

Reovirus-induced apoptosis requires both death receptor- and mitochondrial-mediated caspase-dependent pathways of

D J Kominsky1, R J Bickel, K L Tyler

  • 1Department of Neurology, University of Colorado Health Science Center, Denver, Colorado 80262, USA.

Cell Death and Differentiation
|August 16, 2002
PubMed

Insights

Viral infections trigger apoptosis, but the exact pathways remain unclear. This study details caspase activation during reovirus infection, revealing a biphasic pattern involving both death receptor and mitochondrial pathways.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Apoptosis is crucial in viral pathogenesis, yet the specific mechanisms are not fully understood.
  • Cytoplasmically replicating RNA viruses offer a model to study viral-induced apoptosis.

Purpose of the Study:

  • To characterize caspase activation patterns during reovirus infection.
  • To elucidate the interplay between death receptor and mitochondrial apoptotic pathways in viral infections.

Main Methods:

  • Infection of HEK293 cells with reovirus.
  • Analysis of caspase activation (caspase-8, -9, -3, -7) and substrate cleavage (Bid, PARP).

Main Results:

  • Reovirus infection activated caspase-8, leading to Bid cleavage and mitochondrial pathway initiation.
  • Mitochondrial release of cytochrome c activated caspase-9.
  • Combined death receptor and mitochondrial pathways resulted in effector caspase activation and PARP cleavage.
  • A biphasic activation pattern was observed for caspase-8, Bid, and caspase-3.

Conclusions:

  • Viral infection initiates apoptosis via death receptor pathways, amplified by mitochondrial pathways.
  • This results in a sequential and biphasic caspase activation cascade.
  • Understanding these pathways is key to comprehending viral pathogenesis.

More Related Videos

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

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...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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.
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
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...
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...