Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates
Mammalian cells possess mechanisms to detect and defend themselves from invading viruses. In the cytosol, the RIG-I-like receptors (RLRs), RIG-I (retinoic acid-inducible gene I; encoded by DDX58) and MDA5 (melanoma differentiation-associated gene 5; encoded by IFIH1) sense atypical RNAs associated with virus infection. Detection triggers a signalling cascade via the adaptor MAVS that culminates in the production of type I interferons (IFN-α and β; hereafter IFN), which are key antiviral cytokines. RIG-I and MDA5 are activated by distinct viral RNA structures and much evidence indicates that RIG-I responds to RNAs bearing a triphosphate (ppp) moiety in conjunction with a blunt-ended, base-paired region at the 5'-end (reviewed in refs 1, 2, 3). Here we show that RIG-I also mediates antiviral responses to RNAs bearing 5'-diphosphates (5'pp). Genomes from mammalian reoviruses with 5'pp termini, 5'pp-RNA isolated from yeast L-A virus, and base-paired 5'pp-RNAs made by in vitro transcription or chemical synthesis, all bind to RIG-I and serve as RIG-I agonists. Furthermore, a RIG-I-dependent response to 5'pp-RNA is essential for controlling reovirus infection in cultured cells and in mice. Thus, the minimal determinant for RIG-I recognition is a base-paired RNA with 5'pp. Such RNAs are found in some viruses but not in uninfected cells, indicating that recognition of 5'pp-RNA, like that of 5'ppp-RNA, acts as a powerful means of self/non-self discrimination by the innate immune system.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:514 |
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| Enthalten in: |
Nature - 514(2014), 7522 vom: 16. Okt., Seite 372-375 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Goubau, Delphine [VerfasserIn] |
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| Links: |
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| Themen: |
DEAD Box Protein 58 |
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| Anmerkungen: |
Date Completed 12.11.2014 Date Revised 10.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/nature13590 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM240938313 |
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| 100 | 1 | |a Goubau, Delphine |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates |
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| 500 | |a Date Completed 12.11.2014 | ||
| 500 | |a Date Revised 10.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Mammalian cells possess mechanisms to detect and defend themselves from invading viruses. In the cytosol, the RIG-I-like receptors (RLRs), RIG-I (retinoic acid-inducible gene I; encoded by DDX58) and MDA5 (melanoma differentiation-associated gene 5; encoded by IFIH1) sense atypical RNAs associated with virus infection. Detection triggers a signalling cascade via the adaptor MAVS that culminates in the production of type I interferons (IFN-α and β; hereafter IFN), which are key antiviral cytokines. RIG-I and MDA5 are activated by distinct viral RNA structures and much evidence indicates that RIG-I responds to RNAs bearing a triphosphate (ppp) moiety in conjunction with a blunt-ended, base-paired region at the 5'-end (reviewed in refs 1, 2, 3). Here we show that RIG-I also mediates antiviral responses to RNAs bearing 5'-diphosphates (5'pp). Genomes from mammalian reoviruses with 5'pp termini, 5'pp-RNA isolated from yeast L-A virus, and base-paired 5'pp-RNAs made by in vitro transcription or chemical synthesis, all bind to RIG-I and serve as RIG-I agonists. Furthermore, a RIG-I-dependent response to 5'pp-RNA is essential for controlling reovirus infection in cultured cells and in mice. Thus, the minimal determinant for RIG-I recognition is a base-paired RNA with 5'pp. Such RNAs are found in some viruses but not in uninfected cells, indicating that recognition of 5'pp-RNA, like that of 5'ppp-RNA, acts as a powerful means of self/non-self discrimination by the innate immune system | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Schlee, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Deddouche, Safia |e verfasserin |4 aut | |
| 700 | 1 | |a Pruijssers, Andrea J |e verfasserin |4 aut | |
| 700 | 1 | |a Zillinger, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Goldeck, Marion |e verfasserin |4 aut | |
| 700 | 1 | |a Schuberth, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Van der Veen, Annemarthe G |e verfasserin |4 aut | |
| 700 | 1 | |a Fujimura, Tsutomu |e verfasserin |4 aut | |
| 700 | 1 | |a Rehwinkel, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Iskarpatyoti, Jason A |e verfasserin |4 aut | |
| 700 | 1 | |a Barchet, Winfried |e verfasserin |4 aut | |
| 700 | 1 | |a Ludwig, Janos |e verfasserin |4 aut | |
| 700 | 1 | |a Dermody, Terence S |e verfasserin |4 aut | |
| 700 | 1 | |a Hartmann, Gunther |e verfasserin |4 aut | |
| 700 | 1 | |a Reis e Sousa, Caetano |e verfasserin |4 aut | |
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