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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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180, 2034-2038
|Abstract »|Full Text »|PDF »
CXCR3 Mediates Region-Specific Antiviral T Cell Trafficking within the Central Nervous System during West Nile Virus Encephalitis.
B. Zhang, Y. K. Chan, B. Lu, M. S. Diamond, and R. S. Klein (2008)
J. Immunol.
180, 2641-2649
|Abstract »|Full Text »|PDF »
Acute Lower Respiratory Tract Infection.
J. P. Mizgerd (2008)
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358, 716-727
|Full Text »|PDF »
Short-hairpin RNAs synthesized by T7 phage polymerase do not induce interferon.
T. Gondai, K. Yamaguchi, N. Miyano-Kurosaki, Y. Habu, and H. Takaku (2008)
Nucleic Acids Res.
36, e18
|Abstract »|Full Text »|PDF »
A Single-Amino-Acid Substitution in the NS1 Protein Changes the Pathogenicity of H5N1 Avian Influenza Viruses in Mice.
P. Jiao, G. Tian, Y. Li, G. Deng, Y. Jiang, C. Liu, W. Liu, Z. Bu, Y. Kawaoka, and H. Chen (2008)
J. Virol.
82, 1146-1154
|Abstract »|Full Text »|PDF »
Negative Feedback Regulation of RIG-I-Mediated Antiviral Signaling by Interferon-Induced ISG15 Conjugation.
M.-J. Kim, S.-Y. Hwang, T. Imaizumi, and J.-Y. Yoo (2008)
J. Virol.
82, 1474-1483
|Abstract »|Full Text »|PDF »
