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Published Online October 12, 2006
Science DOI: 10.1126/science.1132998

Reports

Submitted on July 25, 2006
Accepted on October 2, 2006

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 Sousa 1*

1 Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, UK.
2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
3 Department of Virology, University of Freiburg, Freiburg, Germany.

* To whom correspondence should be addressed.
Caetano Reis e Sousa , E-mail: caetano{at}cancer.org.uk

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 RIG-I and MDA5. Here, we show that influenza A virus infection does not generate dsRNA and that RIG-I is activated by single stranded (ss) viral genomic RNA bearing 5' phosphates. This is blocked by the influenza protein 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 uncapped RNA evolved as a means of self/nonself discrimination by the innate immune system.


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   Abstract »    Full Text »    PDF »
MDA5 Participates in the Detection of Paramyxovirus Infection and Is Essential for the Early Activation of Dendritic Cells in Response to Sendai Virus Defective Interfering Particles.
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 »

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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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