Related Experiment Video

Updated: Jun 5, 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

Activation of IFN-β expression by a viral mRNA through RNase L and MDA5

Priya Luthra1, Dengyun Sun, Robert H Silverman

  • 1Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 20, 2011
PubMed

Insights

Researchers discovered a viral messenger RNA (mRNA) from parainfluenza virus 5 (PIV5) that activates type I interferon (IFN) expression. This pathway involves Melanoma differentiation-associated protein 5 (MDA5) and the enzyme RNase L.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Type I interferons (IFNs) are crucial for innate immunity against viral infections.
  • Melanoma differentiation-associated protein 5 (MDA5) is an RNA helicase that senses viral RNA and triggers IFN production.
  • While synthetic double-stranded RNAs activate MDA5, natural single-stranded RNAs have not been previously reported to do so.

Purpose of the Study:

  • To investigate the activation of IFN expression by viral RNA.
  • To identify the specific viral component responsible for MDA5 activation.
  • To elucidate the signaling pathway involved in this immune response.

Main Methods:

  • Identification and characterization of viral RNA from parainfluenza virus 5 (PIV5).
  • Assays to measure IFN-β expression.
  • Mapping of the RNA region responsible for MDA5 activation.
  • Investigation of the role of RNase L in the signaling pathway.

Main Results:

  • A viral mRNA from PIV5 was identified as an activator of IFN expression through MDA5.
  • The L mRNA of PIV5 was shown to activate IFN-β expression.
  • The signaling pathway was found to involve the antiviral enzyme RNase L.
  • A specific 430-nucleotide region within the PIV5 L mRNA was mapped as the activating element.
  • This viral mRNA possesses a 5'-cap and 3'-poly(A) tail.

Conclusions:

  • A naturally occurring viral mRNA can activate IFN expression via the RNase L-MDA5 pathway.
  • This finding expands the understanding of how MDA5 recognizes viral RNA.
  • The study reveals a novel mechanism of innate immune activation by viral mRNA.

More Related Videos

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF311:44

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

Published on: January 24, 2016

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

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...
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...
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...
siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...