Cited by 3,888interferon and immune responsesImmune Response and InflammationRNA regulation and disease

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Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses

Kato, Hiroki, Takeuchi, Osamu, Sato, Shintaro, Yoneyama, Mitsutoshi, Yamamoto, Masahiro, Matsui, Kosuke, Uematsu, Satoshi, Jung, Andreas, Kawai, Taro, Ishii, Ken J., Yamaguchi, Osamu, Otsu, Kinya, Tsujimura, Tohru, Koh, Chang-Sung, Reis e Sousa, Caetano, Matsuura, Yoshiharu, Fujita, Takashi, Akira, Shizuo·2006·Nature

DOI 10.1038/nature04734

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Abstract

The innate immune system senses viral infection by recognizing a variety of viral components (including double-stranded (ds)RNA) and triggers antiviral responses. 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. In vitro studies suggest that both RIG-I and MDA5 detect RNA viruses and polyinosine-polycytidylic acid (poly(I:C)), a synthetic dsRNA analogue. Although a critical role for RIG-I in the recognition of several RNA viruses has been clarified, 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.

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Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
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Authors: Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., Yamaguchi, O., Otsu, K., Tsujimura, T., Koh, C.-S., Reis e Sousa, C., Matsuura, Y., Fujita, T., & Akira, S.
Affiliations: Research Institute for Microbial Diseases, The University of Osaka (JP)
Japan Science and Technology Agency (JP)
Kyoto University (JP)
The University of Osaka (JP)
Hyogo Medical University (JP)
Shinshu University (JP)
Corresponding author: Akira, Shizuo
ORCID: Kato, Hiroki
Takeuchi, Osamu
Sato, Shintaro
Yoneyama, Mitsutoshi
Yamamoto, Masahiro
Uematsu, Satoshi
Kawai, Taro
Ishii, Ken J.
Yamaguchi, Osamu
Otsu, Kinya
Tsujimura, Tohru
Matsuura, Yoshiharu
Fujita, Takashi
Akira, Shizuo
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2006-04-09
Volume: 441
Issue: 7089
Pages: 101-105
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature04734
OpenAlex: W2028575270
Cited by: 3,888
References: 28
Citations by year: 2026: 143 · 2025: 156 · 2024: 146 · 2023: 163 · 2022: 176 · 2021: 204 · 2020: 182 · 2019: 169 · 2018: 169 · 2017: 175 · 2016: 169 · 2015: 182 · 2014: 233 · 2013: 218 · 2012: 236
FWCI: 88.17
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords: MDA5, RIG-I, double-stranded RNA recognition, antiviral innate immunity, interferon production, poly(I:C), paramyxovirus, influenza virus, Japanese encephalitis virus, picornavirus, viral susceptibility
MeSH terms: DEAD Box Protein 58, Interferon-Induced Helicase, IFIH1, Animals, Encephalitis Virus, Japanese, Encephalomyocarditis virus, Immunity, Innate, RNA Viruses, RNA, Double-Stranded, RNA, Viral, RNA Helicases, Mice, DEAD-box RNA Helicases

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Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses

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