RIG-I-Mediated Antiviral Responses to Single-Stranded RNA Bearing 5'-Phosphates

Andreas Pichlmair, Oliver Schulz, Choon Ping Tan, Tanja I. Näslund, Peter Liljeström, Friedemann Weber, Caetano Reis e Sousa

doi:10.1126/science.1132998

RIG-I-Mediated Antiviral Responses to Single-Stranded RNA Bearing 5'-Phosphates

DOI Web Site 被引用文献89件

Andreas Pichlmair

Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
Oliver Schulz

Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
Choon Ping Tan

Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
Tanja I. Näslund

Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
Peter Liljeström

Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
Friedemann Weber

Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
Caetano Reis e Sousa

Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.

抄録

<jats:p>Double-stranded RNA (dsRNA) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the RNA helicase enzymes retinoic acid–inducible gene I (RIG-I) and melanoma differentiation–associated gene 5 (MDA5). We showed that influenza A virus infection does not generate dsRNA and that RIG-I is activated by viral genomic single-stranded RNA (ssRNA) bearing 5′-phosphates. This is blocked by the influenza protein nonstructured protein 1 (NS1), which is found in a complex with RIG-I in infected cells. These results identify RIG-I as a ssRNA sensor and potential target of viral immune evasion and suggest that its ability to sense 5'-phosphorylated RNA evolved in the innate immune system as a means of discriminating between self and nonself.</jats:p>