IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v441y2006i7089d10.1038_nature04734.html
   My bibliography  Save this article

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

Author

Listed:
  • Hiroki Kato

    (Department of Host Defense
    ERATO, Japan Science and Technology Agency)

  • Osamu Takeuchi

    (Department of Host Defense
    ERATO, Japan Science and Technology Agency)

  • Shintaro Sato

    (ERATO, Japan Science and Technology Agency)

  • Mitsutoshi Yoneyama

    (Kyoto University)

  • Masahiro Yamamoto

    (Department of Host Defense)

  • Kosuke Matsui

    (Department of Host Defense)

  • Satoshi Uematsu

    (Department of Host Defense)

  • Andreas Jung

    (Department of Host Defense)

  • Taro Kawai

    (ERATO, Japan Science and Technology Agency)

  • Ken J. Ishii

    (ERATO, Japan Science and Technology Agency)

  • Osamu Yamaguchi

    (Osaka University Graduate School of Medicine)

  • Kinya Otsu

    (Osaka University Graduate School of Medicine)

  • Tohru Tsujimura

    (Hyogo College of Medicine)

  • Chang-Sung Koh

    (Shinshu University School of Allied Medical Sciences)

  • Caetano Reis e Sousa

    (Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories)

  • Yoshiharu Matsuura

    (Research Institute for Microbial Diseases, University)

  • Takashi Fujita

    (Kyoto University)

  • Shizuo Akira

    (Department of Host Defense
    ERATO, Japan Science and Technology Agency)

Abstract

The innate immune system senses viral infection by recognizing a variety of viral components (including double-stranded (ds)RNA) and triggers antiviral responses1,2. 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 recognition3,4,5,6,7. In vitro studies suggest that both RIG-I and MDA5 detect RNA viruses and polyinosine-polycytidylic acid (poly(I:C)), a synthetic dsRNA analogue3. Although a critical role for RIG-I in the recognition of several RNA viruses has been clarified8, 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.

Suggested Citation

  • Hiroki Kato & Osamu Takeuchi & Shintaro Sato & Mitsutoshi Yoneyama & Masahiro Yamamoto & Kosuke Matsui & Satoshi Uematsu & Andreas Jung & Taro Kawai & Ken J. Ishii & Osamu Yamaguchi & Kinya Otsu & Toh, 2006. "Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses," Nature, Nature, vol. 441(7089), pages 101-105, May.
  • Handle: RePEc:nat:nature:v:441:y:2006:i:7089:d:10.1038_nature04734
    DOI: 10.1038/nature04734
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature04734
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/nature04734?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Duomeng Yang & Tingting Geng & Andrew G. Harrison & Jason G. Cahoon & Jian Xing & Baihai Jiao & Mark Wang & Chao Cheng & Robert E. Hill & Huadong Wang & Anthony T. Vella & Gong Cheng & Yanlin Wang & P, 2024. "UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Yongfang Lin & Jing Yang & Qili Yang & Sha Zeng & Jiayu Zhang & Yuanxiang Zhu & Yuxin Tong & Lin Li & Weiqi Tan & Dahua Chen & Qinmiao Sun, 2023. "PTK2B promotes TBK1 and STING oligomerization and enhances the STING-TBK1 signaling," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Qin Yu & Alba Herrero del Valle & Rahul Singh & Yorgo Modis, 2021. "MDA5 disease variant M854K prevents ATP-dependent structural discrimination of viral and cellular RNA," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    4. Ning Yang & Joseph M. Luna & Peihong Dai & Yi Wang & Charles M. Rice & Liang Deng, 2022. "Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against poxvirus infection," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Lindsey E. Bazzone & Junji Zhu & Michael King & GuanQun Liu & Zhiru Guo & Christopher R. MacKay & Pyae P. Kyawe & Natasha Qaisar & Joselyn Rojas-Quintero & Caroline A. Owen & Abraham L. Brass & Willia, 2024. "ADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    6. Janelle M Veazey & Timothy J Chapman & Timothy R Smyth & Sara E Hillman & Sophia I Eliseeva & Steve N Georas, 2019. "Distinct roles for MDA5 and TLR3 in the acute response to inhaled double-stranded RNA," PLOS ONE, Public Library of Science, vol. 14(5), pages 1-16, May.
    7. Seethalakshmi Hariharan & Benjamin T. Whitfield & Christopher J. Pirozzi & Matthew S. Waitkus & Michael C. Brown & Michelle L. Bowie & David M. Irvin & Kristen Roso & Rebecca Fuller & Janell Hostettle, 2024. "Interplay between ATRX and IDH1 mutations governs innate immune responses in diffuse gliomas," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:441:y:2006:i:7089:d:10.1038_nature04734. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.