Related Experiment Video

Updated: Apr 26, 2026

Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
12:43

Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE

Published on: July 29, 2014

11.6K

PKR condensation at viral replication complexes initiates its activation

Ebba K Blomqvist1, Nicole Bracci2, Helena Winstone2

  • 1Department of Molecular Medicine, The Herbert Wertheim University of Florida Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL 33458, USA; Department of Immunology and Microbiology, The Herbert Wertheim University of Florida Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL 33458, USA; Skaggs Graduate School of Chemical and Biological Sciences, The Scripps Research Institute, Jupiter, FL 33458, USA.

Cell Reports
|April 24, 2026
PubMed

Insights

Protein kinase R (PKR) activates by condensing on viral RNA, then dissolving to trigger antiviral immunity. This process allows continuous activation, though MERS-CoV can block it.

Area of Science:

  • Virology
  • Immunology
  • Cellular Biology

Background:

  • Protein kinase R (PKR) is essential for mammalian innate antiviral defense.
  • Understanding PKR activation mechanisms is crucial for developing antiviral strategies.

Purpose of the Study:

  • To elucidate the activation process of Protein kinase R (PKR) in response to MERS-CoV and ZIKV.
  • To investigate the role of viral replication complexes in PKR activation.
  • To identify viral factors that modulate PKR activation.

Main Methods:

  • Super-resolution confocal microscopy
  • Proximity ligation assay
  • Immunogold transmission electron microscopy
  • Live-cell imaging

Main Results:

  • PKR activation occurs via condensation on double-stranded RNA (dsRNA) within viral replication complexes.
  • Activated PKR condensates dissolve, releasing PKR to phosphorylate eIF2α and initiate the integrated stress response (ISR).
  • MERS-CoV NS4a protein inhibits PKR activation by competitively binding to viral dsRNA.

Conclusions:

  • A detailed model for PKR activation by positive-strand RNA viruses replicating in membrane-associated complexes is established.
  • PKR's dynamic condensation and dissolution mechanism allows amplification of antiviral signaling.
  • Viral evasion strategies, like MERS-CoV NS4a interference, highlight the importance of PKR in antiviral immunity.
Keywords:
CP: microbiologyCP: molecular biologyDRIFMERS-CoVNS4aPKRZika viruscondensationdsRNAinnate immunitynsp15viral antagonist proteins

More Related Videos

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle10:05

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle

Published on: March 5, 2019

6.1K
Functional Imaging of Viral Transcription Factories Using 3D Fluorescence Microscopy09:03

Functional Imaging of Viral Transcription Factories Using 3D Fluorescence Microscopy

Published on: January 18, 2018

6.3K

Related Concept Videos

S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.7K
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

3.0K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.3K
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...
55
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
15.5K
Transcription Initiation01:47

Transcription Initiation

Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
The promoters and enhancers and their accessory proteins allow tight regulation of...
16.9K