Related Experiment Video

Updated: May 11, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
11:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

MDA5 plays a crucial role in enterovirus 71 RNA-mediated IRF3 activation

Rei-Lin Kuo1, Li-Ting Kao, Sue-Jane Lin

  • 1Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Gueishan, Tao-Yuan, Taiwan. rlkuo@mail.cgu.edu.tw

Plos One
|May 8, 2013
PubMed

Insights

Melanoma differentiation-associated gene 5 (MDA5) recognizes Enterovirus 71 (EV71) RNA, activating innate immune responses. EV71 infection degrades MDA5, but this can be blocked, highlighting MDA5

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Type-I interferons (IFNs) are vital for innate immunity against RNA viruses.
  • RIG-I-like receptors (RLRs), including RIG-I and MDA5, sense viral RNA and trigger IFN production.
  • MDA5 is known to be essential for type-I IFN induction by certain picornaviruses.

Purpose of the Study:

  • To elucidate the specific cytoplasmic RIG-I-like receptor involved in recognizing Enterovirus 71 (EV71) RNA.
  • To investigate the role of MDA5 in the innate immune response to EV71 infection.
  • To understand the mechanisms by which EV71 might evade MDA5-mediated antiviral signaling.

Main Methods:

  • Utilized EV71-derived RNA as an agonist to stimulate cellular responses.
  • Assessed Interferon Regulatory Factor 3 (IRF3) activation and IFN-β transcription.
  • Examined the effect of EV71 infection on MDA5 protein levels and degradation.
  • Tested the impact of a broad-spectrum caspase inhibitor on MDA5 degradation.

Main Results:

  • EV71-derived RNA activates MDA5, leading to IRF3 activation and IFN-β transcription.
  • Overexpression of MDA5 protein can counteract the suppression of IRF3 activation caused by EV71 infection.
  • EV71 infection promotes the degradation of MDA5.
  • Inhibition of caspases can prevent EV71-induced MDA5 degradation.

Conclusions:

  • MDA5 is a critical sensor for EV71 RNA, playing a key role in activating type-I IFN expression.
  • EV71 employs a mechanism involving MDA5 degradation to potentially evade innate immune detection.
  • Targeting MDA5 degradation pathways may offer therapeutic strategies against EV71 infections.

More Related Videos

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization08:57

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization

Published on: October 6, 2019

Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE12:43

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

Published on: July 29, 2014

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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 stands for...
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...
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...