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RIG-I-Mediated Antiviral Responses to Single-Stranded RNA Bearing 5'-Phosphates
Andreas Pichlmair,1Oliver Schulz,1Choon Ping Tan,1Tanja I. Näslund,2Peter Liljeström,2Friedemann Weber,3Caetano Reis e Sousa1*
Double-stranded RNA (dsRNA) produced during viral replicationis believed to be the critical trigger for activation of antiviralimmunity mediated by the RNA helicase enzymes retinoic acid–induciblegene I (RIG-I) and melanoma differentiation–associatedgene 5 (MDA5). We showed that influenza A virus infection doesnot generate dsRNA and that RIG-I is activated by viral genomicsingle-stranded RNA (ssRNA) bearing 5'-phosphates. This is blockedby the influenza protein nonstructured protein 1 (NS1), whichis found in a complex with RIG-I in infected cells. These resultsidentify RIG-I as a ssRNA sensor and potential target of viralimmune evasion and suggest that its ability to sense 5'-phosphorylatedRNA evolved in the innate immune system as a means of discriminatingbetween self and nonself.
1 Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK. 2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden. 3 Department of Virology, University of Freiburg, Freiburg 79104, Germany.
* To whom correspondence should be addressed. E-mail: caetano{at}cancer.org.uk
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