Journal ArticleDOI
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Hiroki Kato,Osamu Takeuchi,Shintaro Sato,Mitsutoshi Yoneyama,Masahiro Yamamoto,Kosuke Matsui,Satoshi Uematsu,Andreas Jung,Taro Kawai,Ken Ishii,Osamu Yamaguchi,Kinya Otsu,Tohru Tsujimura,Chang-Sung Koh,Caetano Reis e Sousa,Yoshiharu Matsuura,Takashi Fujita,Shizuo Akira +17 more
TLDR
It is found 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.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.read more
Citations
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Journal ArticleDOI
Pattern Recognition Receptors and Inflammation
Osamu Takeuchi,Shizuo Akira +1 more
TL;DR: The role of PRRs, their signaling pathways, and how they control inflammatory responses are discussed.
Journal ArticleDOI
Toll-like receptors.
TL;DR: This unit discusses mammalian Toll receptors (TLR1‐10) that have an essential role in the innate immune recognition of microorganisms and are discussed are TLR‐mediated signaling pathways and antibodies that are available to detect specific TLRs.
Journal ArticleDOI
Recognition of microorganisms and activation of the immune response.
TL;DR: The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections, and recent progress brings us closer to an integrated view of the immune system and its function in host defence.
Journal ArticleDOI
Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses
TL;DR: This review presents current knowledge on pathogen recognition through different families of PRRs and the increasingly complex signaling pathways responsible for activation of an inflammatory and antimicrobial response and medical implications are discussed.
Journal ArticleDOI
5'-Triphosphate RNA Is the Ligand for RIG-I
Veit Hornung,Jana M. Ellegast,Sarah Kim,Krzysztof Brzózka,Andreas Jung,Hiroki Kato,Hendrik Poeck,Shizuo Akira,Karl-Klaus Conzelmann,Martin Schlee,Stefan Endres,Gunther Hartmann +11 more
TL;DR: It is demonstrated that the 5′-triphosphate end of RNA generated by viral polymerases is responsible for retinoic acid–inducible protein I (RIG-I)–mediated detection of RNA molecules in viruses known to be detected by MDA-5 such as the picornaviruses.
References
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Journal ArticleDOI
Pathogen Recognition and Innate Immunity
TL;DR: New insights into innate immunity are changing the way the way the authors think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.
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Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3.
TL;DR: It is shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB and the production of type I interferons (IFNs).
Journal ArticleDOI
Toll-like receptor control of the adaptive immune responses.
Akiko Iwasaki,Ruslan Medzhitov +1 more
TL;DR: Recognition of microbial infection and initiation of host defense responses is controlled by multiple mechanisms and recent studies have provided important clues about the mechanisms of TLR-mediated control of adaptive immunity orchestrated by dendritic cell populations in distinct anatomical locations.
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The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.
Mitsutoshi Yoneyama,Mika Kikuchi,Takashi Natsukawa,Noriaki Shinobu,Tadaatsu Imaizumi,Makoto Miyagishi,Kazunari Taira,Shizuo Akira,Takashi Fujita +8 more
TL;DR: In this article, the authors identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling.
Journal ArticleDOI
Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA.
TL;DR: These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.