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Originally published in Science Express on 12 October 2006
Science 10 November 2006:
Vol. 314. no. 5801, pp. 997 - 1001
DOI: 10.1126/science.1132998

Reports

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*

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. S. Yount, L. Gitlin, T. M. Moran, and C. B. Lopez (2008)
J. Immunol. 180, 4910-4918
   Abstract »    Full Text »    PDF »
NFAR-1 and -2 modulate translation and are required for efficient host defense.
I. Pfeifer, R. Elsby, M. Fernandez, P. A. Faria, D. R. Nussenzveig, I. S. Lossos, B. M. A. Fontoura, W. D. Martin, and G. N. Barber (2008)
PNAS 105, 4173-4178
   Abstract »    Full Text »    PDF »
Alpha/Beta Interferon Inhibits Cap-Dependent Translation of Viral but Not Cellular mRNA by a PKR-Independent Mechanism.
M. Z. Tesfay, J. Yin, C. L. Gardner, M. V. Khoretonenko, N. L. Korneeva, R. E. Rhoads, K. D. Ryman, and W. B. Klimstra (2008)
J. Virol. 82, 2620-2630
   Abstract »    Full Text »    PDF »
Phagocytosis of Picornavirus-Infected Cells Induces an RNA-Dependent Antiviral State in Human Dendritic Cells.
M. Kramer, B. M. Schulte, L. W. J. Toonen, P. M. Barral, P. B. Fisher, K. H. W. Lanke, J. M. D. Galama, F. J. M. van Kuppeveld, and G. J. Adema (2008)
J. Virol. 82, 2930-2937
   Abstract »    Full Text »    PDF »
Human Lymphatic Endothelial Cells Express Multiple Functional TLRs.
A. Pegu, S. Qin, B. A. Fallert Junecko, R. E. Nisato, M. S. Pepper, and T. A. Reinhart (2008)
J. Immunol. 180, 3399-3405
   Abstract »    Full Text »    PDF »
Avian and 1918 Spanish Influenza A Virus NS1 Proteins Bind to Crk/CrkL Src Homology 3 Domains to Activate Host Cell Signaling.
L. S. Heikkinen, A. Kazlauskas, K. Melen, R. Wagner, T. Ziegler, I. Julkunen, and K. Saksela (2008)
J. Biol. Chem. 283, 5719-5727
   Abstract »    Full Text »    PDF »
Independent and Cooperative Antiviral Actions of Beta Interferon and Gamma Interferon against Herpes Simplex Virus Replication in Primary Human Fibroblasts.
T. Peng, J. Zhu, Y. Hwangbo, L. Corey, and R. E. Bumgarner (2008)
J. Virol. 82, 1934-1945
   Abstract »    Full Text »    PDF »
Cutting Edge: Innate Immune Response Triggered by Influenza A Virus Is Negatively Regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-Dependent Pathway.
J. Pothlichet, M. Chignard, and M. Si-Tahar (2008)
J. Immunol. 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)
N. Engl. J. Med. 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 »

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Low Level Expression of RIG-1 in Human Lung Epithelium Allows Influenza Virus to Replicate
Syed H. I. Abidi
Science Online, 4 Apr 2007 [Full text]



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