Related Experiment Video

Updated: Oct 21, 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

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Differential roles of RIG-I like receptors in SARS-CoV-2 infection

Duo-Meng Yang1, Ting-Ting Geng1, Andrew G Harrison1

  • 1Department of Immunology, School of Medicine, University of Connecticut Health Center, Farmington, CT, 06030, USA.

Military Medical Research
|September 7, 2021
PubMed

Insights

Melanoma differentiation-associated protein 5 (MDA5) is the main sensor for SARS-CoV-2 in epithelial cells, triggering immune responses. Retinoic acid-inducible gene I (RIG-I) also plays a role in controlling viral entry receptor ACE2.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) are key pattern recognition receptors sensing viral RNA.
  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects human epithelial cells, initiating innate immune responses.
  • Mitochondrial antiviral signaling protein (MAVS) acts as a crucial adaptor protein in RIG-I and MDA5 signaling pathways.

Discussion:

  • MDA5 deficiency significantly impairs type I/III interferon (IFN) expression during SARS-CoV-2 infection, highlighting its predominant role in sensing the virus.
  • RIG-I deficiency leads to increased angiotensin-converting enzyme 2 (ACE2) mRNA levels, suggesting an IFN-independent mechanism by which RIG-I regulates viral entry receptor expression.
  • MAVS deficiency similarly impairs IFN responses, underscoring its central role in downstream signaling for both RIG-I and MDA5.

Key Insights:

  • MDA5 is identified as the primary sensor for SARS-CoV-2 in human epithelial cells.
  • RIG-I exhibits an anti-SARS-CoV-2 function by negatively regulating ACE2 expression in an IFN-independent manner.
  • MAVS is essential for robust type I/III IFN responses to SARS-CoV-2 infection.

Outlook:

  • Further investigation into the specific viral RNA structures recognized by MDA5 and RIG-I in the context of SARS-CoV-2.
  • Exploring therapeutic strategies targeting RIG-I or MDA5 pathways to enhance epithelial cell antiviral defenses against SARS-CoV-2.
  • Elucidating the precise mechanism of IFN-independent ACE2 regulation by RIG-I in epithelial cells.
Keywords:
Melanoma differentiation-associated protein 5Pathogen pattern recognition receptorRetinoic acid-inducible gene ISARS-CoV-2

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