Comparative structure and function analysis of the RIG-I-like receptors: RIG-I and MDA5

Morgan Brisse, Hinh Ly

Research output: Contribution to journalReview articlepeer-review

211 Scopus citations


RIG-I (Retinoic acid-inducible gene I) and MDA5 (Melanoma Differentiation-Associated protein 5), collectively known as the RIG-I-like receptors (RLRs), are key protein sensors of the pathogen-associated molecular patterns (PAMPs) in the form of viral doublestranded RNA (dsRNA) motifs to induce expression of type 1 interferons (IFN1) (IFNα and IFNβ) and other pro-inflammatory cytokines during the early stage of viral infection. While RIG-I and MDA5 share many genetic, structural and functional similarities, there is increasing evidence that they can have significantly different strategies to recognize different pathogens, PAMPs, and in different host species. This review article discusses the similarities and differences between RIG-I and MDA5 from multiple perspectives, including their structures, evolution and functional relationships with other cellular proteins, their differential mechanisms of distinguishing between host and viral dsRNAs and interactions with host and viral protein factors, and their immunogenic signaling. A comprehensive comparative analysis can help inform future studies of RIG-I and MDA5 in order to fully understand their functions in order to optimize potential therapeutic approaches targeting them.

Original languageEnglish (US)
Article number1586
JournalFrontiers in immunology
Issue numberJULY
StatePublished - 2019

Bibliographical note

Funding Information:
This work was supported in part by NIH NIAID grant R01 AI131586 to HL and by a pre-doctoral NIH fellowship T32 DA007097 to MB.

Publisher Copyright:
Copyright © 2019 Brisse and Ly. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.


  • Antiviral
  • CARD
  • Inflammation
  • Interferon
  • MDA5
  • PAMP
  • PRRs
  • RIG-I


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