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Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
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Journal Article
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
2006
Overview
The innate immune system senses viral infection by recognizing a variety of viral components (including double-stranded (ds)RNA) and triggers antiviral responses
1
,
2
. The cytoplasmic helicase proteins RIG-I (retinoic-acid-inducible protein I, also known as Ddx58) and MDA5 (melanoma-differentiation-associated gene 5, also known as Ifih1 or Helicard) have been implicated in viral dsRNA recognition
3
,
4
,
5
,
6
,
7
.
In vitro
studies suggest that both RIG-I and MDA5 detect RNA viruses and polyinosine-polycytidylic acid (poly(I:C)), a synthetic dsRNA analogue
3
. Although a critical role for RIG-I in the recognition of several RNA viruses has been clarified
8
, the functional role of MDA5 and the relationship between these dsRNA detectors
in vivo
are yet to be determined. Here we use mice deficient in MDA5 (
MDA5
-/-
) to show that MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects
in vitro
transcribed dsRNAs. RNA viruses are also differentially recognized by RIG-I and MDA5. We find that RIG-I is essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza virus and Japanese encephalitis virus, whereas MDA5 is critical for picornavirus detection. Furthermore,
RIG-I
-/-
and
MDA5
-/-
mice are highly susceptible to infection with these respective RNA viruses compared to control mice. Together, our data show that RIG-I and MDA5 distinguish different RNA viruses and are critical for host antiviral responses.
Publisher
Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
Subject
/ Biological and medical sciences
/ Encephalitis Virus, Japanese - immunology
/ Encephalomyocarditis virus - immunology
/ Fundamental and applied biological sciences. Psychology
/ Humanities and Social Sciences
/ Immunity, Innate - immunology
/ Interferon-Induced Helicase, IFIH1
/ letter
/ Melanoma
/ Mice
/ Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains
/ RNA
/ RNA Viruses - classification
/ RNA, Double-Stranded - genetics
/ RNA, Double-Stranded - immunology
/ Rodents
/ Science
/ Virology
/ Viruses
