Abstract
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.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Animals
- Cell Line
- Cells, Cultured
- Cytoplasm / metabolism
- Cytoplasm / virology
- DEAD Box Protein 58
- DEAD-box RNA Helicases / genetics
- DEAD-box RNA Helicases / metabolism*
- Dendritic Cells / virology
- Encephalomyocarditis virus / genetics
- Encephalomyocarditis virus / immunology
- Encephalomyocarditis virus / metabolism
- Genome, Viral
- Humans
- Immunity, Innate*
- Influenza A virus / genetics*
- Influenza A virus / immunology*
- Influenza A virus / metabolism
- Influenza A virus / physiology
- Interferon-alpha / biosynthesis
- Interferon-beta / biosynthesis
- Mice
- Mice, Inbred C57BL
- Phosphates / metabolism
- Phosphorylation
- RNA Caps / metabolism
- RNA, Double-Stranded / metabolism
- RNA, Viral / chemistry
- RNA, Viral / genetics
- RNA, Viral / metabolism*
- Receptors, Immunologic
- Recombinant Fusion Proteins / metabolism
- Transfection
- Vesicular stomatitis Indiana virus / genetics
- Vesicular stomatitis Indiana virus / immunology
- Vesicular stomatitis Indiana virus / metabolism
- Viral Nonstructural Proteins / genetics
- Viral Nonstructural Proteins / metabolism
- Virus Replication
Substances
- INS1 protein, influenza virus
- Interferon-alpha
- Phosphates
- RNA Caps
- RNA, Double-Stranded
- RNA, Viral
- Receptors, Immunologic
- Recombinant Fusion Proteins
- Viral Nonstructural Proteins
- Interferon-beta
- RIGI protein, human
- DEAD Box Protein 58
- DEAD-box RNA Helicases