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The Journal of Immunology, 2005, 175: 5260-5268.
Copyright © 2005 by The American Association of Immunologists

The RNA Helicase Lgp2 Inhibits TLR-Independent Sensing of Viral Replication by Retinoic Acid-Inducible Gene-I1

Simon Rothenfusser2,*, Nadege Goutagny2,*, Gary DiPerna*, Mei Gong*, Brian G. Monks*, Annett Schoenemeyer*, Masahiro Yamamoto{dagger}, Shizuo Akira{dagger} and Katherine A. Fitzgerald3,*

* Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605; and {dagger} Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

The paramyxovirus Sendai (SV), is a well-established inducer of IFN-{alpha}{beta} gene expression. In this study we show that SV induces IFN-{alpha}{beta} gene expression normally in cells from mice with targeted deletions of the Toll-IL-1 resistance domain containing adapters MyD88, Mal, Toll/IL-1R domain-containing adaptor inducing IFN-{beta} (TRIF), and TRIF-related adaptor molecule TLR3, or the E3 ubiquitin ligase, TNFR-associated factor 6. This TLR-independent induction of IFN-{alpha}{beta} after SV infection is replication dependent and mediated by the RNA helicase, retinoic acid-inducible gene-I (RIG-I) and not the related family member, melanoma differentiation-associated gene 5. Furthermore, we characterize a RIG-I-like RNA helicase, Lgp2. In contrast to RIG-I or melanoma differentiation-associated gene 5, Lgp2 lacks signaling caspase recruitment and activation domains. Overexpression of Lgp2 inhibits SV and Newcastle disease virus signaling to IFN-stimulated regulatory element- and NF-{kappa}B-dependent pathways. Importantly, Lgp2 does not prevent TLR3 signaling. Like RIG-I, Lgp2 binds double-stranded, but not single-stranded, RNA. Quantitative PCR analysis demonstrates that Lgp2 is present in unstimulated cells at a lower level than RIG-I, although both helicases are induced to similar levels after virus infection. We propose that Lgp2 acts as a negative feedback regulator of antiviral signaling by sequestering dsRNA from RIG-I.




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Home page
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[Abstract] [Full Text] [PDF]

Home page
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Home page
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J. Biochem., February 1, 2007; 141(2): 137 - 145.
[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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Home page
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[Abstract] [Full Text] [PDF]

Home page
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Science, November 10, 2006; 314(5801): 997 - 1001.
[Abstract] [Full Text] [PDF]

Home page
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J. Biol. Chem., September 8, 2006; 281(36): 26188 - 26195.
[Abstract] [Full Text] [PDF]

Home page
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PNAS, May 30, 2006; 103(22): 8459 - 8464.
[Abstract] [Full Text] [PDF]

Home page
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Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses.
J. Virol., May 1, 2006; 80(10): 5059 - 5064.
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