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Science 314 (5801): 997-1001

Copyright © 2006 by the American Association for the Advancement of Science

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

Andreas Pichlmair,1 Oliver Schulz,1 Choon Ping Tan,1 Tanja I. Näslund,2 Peter Liljeström,2 Friedemann Weber,3 Caetano Reis e Sousa1*

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.

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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J. Melchjorsen, J. Rintahaka, S. Soby, K. A. Horan, A. Poltajainen, L. Ostergaard, S. R. Paludan, and S. Matikainen (2010)
J. Virol. 84, 11350-11358
   Abstract »    Full Text »    PDF »
The ESEV PDZ-Binding Motif of the Avian Influenza A Virus NS1 Protein Protects Infected Cells from Apoptosis by Directly Targeting Scribble.
H. Liu, L. Golebiewski, E. C. Dow, R. M. Krug, R. T. Javier, and A. P. Rice (2010)
J. Virol. 84, 11164-11174
   Abstract »    Full Text »    PDF »
Influenza A Virus Polymerase Inhibits Type I Interferon Induction by Binding to Interferon {beta} Promoter Stimulator 1.
A. Iwai, T. Shiozaki, T. Kawai, S. Akira, Y. Kawaoka, A. Takada, H. Kida, and T. Miyazaki (2010)
J. Biol. Chem. 285, 32064-32074
   Abstract »    Full Text »    PDF »
Inhibition of Hepatitis C Virus Replication by IFN-Mediated ISGylation of HCV-NS5A.
M.-J. Kim and J.-Y. Yoo (2010)
J. Immunol. 185, 4311-4318
   Abstract »    Full Text »    PDF »
Induction and Inhibition of Type I Interferon Responses by Distinct Components of Lymphocytic Choriomeningitis Virus.
S. Zhou, A. M. Cerny, A. Zacharia, K. A. Fitzgerald, E. A. Kurt-Jones, and R. W. Finberg (2010)
J. Virol. 84, 9452-9462
   Abstract »    Full Text »    PDF »
Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing.
A. Baum, R. Sachidanandam, and A. Garcia-Sastre (2010)
PNAS 107, 16303-16308
   Abstract »    Full Text »    PDF »
Activation of the Interferon Response by Human Cytomegalovirus Occurs via Cytoplasmic Double-Stranded DNA but Not Glycoprotein B.
V. R. DeFilippis, T. Sali, D. Alvarado, L. White, W. Bresnahan, and K. J. Fruh (2010)
J. Virol. 84, 8913-8925
   Abstract »    Full Text »    PDF »
The 3C Protein of Enterovirus 71 Inhibits Retinoid Acid-Inducible Gene I-Mediated Interferon Regulatory Factor 3 Activation and Type I Interferon Responses.
X. Lei, X. Liu, Y. Ma, Z. Sun, Y. Yang, Q. Jin, B. He, and J. Wang (2010)
J. Virol. 84, 8051-8061
   Abstract »    Full Text »    PDF »
TLR3 and Rig-Like Receptor on Myeloid Dendritic Cells and Rig-Like Receptor on Human NK Cells Are Both Mandatory for Production of IFN-{gamma} in Response to Double-Stranded RNA.
I. Perrot, F. Deauvieau, C. Massacrier, N. Hughes, P. Garrone, I. Durand, O. Demaria, N. Viaud, L. Gauthier, M. Blery, et al. (2010)
J. Immunol. 185, 2080-2088
   Abstract »    Full Text »    PDF »
Qualitatively Different Memory CD8+ T Cells Are Generated after Lymphocytic Choriomeningitis Virus and Influenza Virus Infections.
S. N. Mueller, W. A. Langley, G. Li, A. Garcia-Sastre, R. J. Webby, and R. Ahmed (2010)
J. Immunol. 185, 2182-2190
   Abstract »    Full Text »    PDF »
Double-stranded RNA-dependent ATPase DRH-3: INSIGHT INTO ITS ROLE IN RNA SILENCING IN CAENORHABDITIS ELEGANS.
C. Matranga and A. M. Pyle (2010)
J. Biol. Chem. 285, 25363-25371
   Abstract »    Full Text »    PDF »
Inefficient Control of Host Gene Expression by the 2009 Pandemic H1N1 Influenza A Virus NS1 Protein.
B. G. Hale, J. Steel, R. A. Medina, B. Manicassamy, J. Ye, D. Hickman, R. Hai, M. Schmolke, A. C. Lowen, D. R. Perez, et al. (2010)
J. Virol. 84, 6909-6922
   Abstract »    Full Text »    PDF »
Avian Bornavirus Associated with Fatal Disease in Psittacine Birds.
P. Staeheli, M. Rinder, and B. Kaspers (2010)
J. Virol. 84, 6269-6275
   Abstract »    Full Text »    PDF »
Negative Role of RIG-I Serine 8 Phosphorylation in the Regulation of Interferon-{beta} Production.
E. Nistal-Villan, M. U. Gack, G. Martinez-Delgado, N. P. Maharaj, K.-S. Inn, H. Yang, R. Wang, A. K. Aggarwal, J. U. Jung, and A. Garcia-Sastre (2010)
J. Biol. Chem. 285, 20252-20261
   Abstract »    Full Text »    PDF »

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