Related Experiment Video

Updated: May 31, 2025

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

12.1K

Regulation of interferon alpha production by the MAGUK-family protein CASK under H5N1 infection

Jing-Ying Huang1,2, Pei-Shan Sung2, Shie-Liang Hsieh2,3,4,5

  • 1Doctoral Degree Program of Translational Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.

Frontiers in Immunology
|January 24, 2025
PubMed

Insights

The study reveals that CASK protein aids nuclear entry in H5N1-infected macrophages, crucial for interferon-alpha (IFNA) production and antiviral defense. CASK deficiency impairs IFNA mRNA export, worsening lung inflammation during H5N1 infection.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • CASK (Calcium/calmodulin-dependent serine protein kinase)-associated protein, a MAGUK family scaffold protein, is known to regulate gene expression as a transcription co-activator in neurons.
  • The precise mechanisms governing CASK nuclear translocation and its function within myeloid cells, particularly during viral infections, remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the role of CASK in H5N1-infected macrophages.
  • To investigate the signaling pathways and molecular interactions involved in CASK nuclear translocation and its regulation of antiviral gene expression.

Main Methods:

  • Investigated CASK nuclear translocation in H5N1-infected macrophages using PKR and SRC signaling pathway analysis.
  • Utilized HCK and CDK5 to study CASK phosphorylation at S395 and its impact on nuclear entry.
  • Generated myeloid-specific CASK knockout (KO) mice to assess the in vivo role of CASK in H5N1 infection and lung inflammation.
  • Performed interactome studies to identify CASK-interacting partners and their role in interferon-alpha (IFNA) gene regulation and mRNA export.

Main Results:

  • H5N1 infection induces CASK nuclear translocation via PKR and SRC signaling pathways.
  • HCK-mediated CASK phosphorylation at S395 by CDK5 facilitates CASK's nuclear entry.
  • Myeloid-specific CASK KO mice exhibit increased lung inflammation and reduced IFNA levels during H5N1 infection.
  • CASK deficiency hinders the nuclear export of Ifna mRNA, impacting antiviral response without altering mRNA levels.

Conclusions:

  • CASK plays a critical role in the antiviral response by facilitating IFNA production in macrophages.
  • CASK nuclear translocation and its complex formation with specific proteins are essential for regulating IFNA gene expression and mRNA export.
  • Targeting CASK may offer therapeutic strategies for managing severe H5N1-induced lung inflammation.
Keywords:
CASKCRM1H5N1influenza A virusinterferon-alphamRNA exportmacrophagenuclear entry

More Related Videos

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

10.4K
Rescue of Recombinant Newcastle Disease Virus from cDNA10:55

Rescue of Recombinant Newcastle Disease Virus from cDNA

Published on: October 11, 2013

19.3K

Related Concept Videos

Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
735
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.1K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K