Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. STKE, 1 May 2007
Vol. 2007, Issue 384, p. pe20
[DOI: 10.1126/stke.3842007pe20]

PERSPECTIVES

Regulation of Interferon Production by RIG-I and LGP2: A Lesson in Self-Control

Damien Vitour and Eliane F. Meurs*

Hepacivirus Unit, Pasteur Institute, Paris Cedex 15, France

Abstract: The cytoplasmic CARD-containing DExD/H box RNA helicases RIG-I and MDA5 act as sensors of viral infections through recognition of viral double-stranded (ds) RNAs. They both associate with the mitochondrial adaptor IPS-1 (also referred to as MAVS, VISA, and CARDIF) through homotypic CARD-CARD interactions. IPS-1, in turn, triggers signaling pathways, including activation of the protein kinases TBK1 and IKK{varepsilon}, responsible for the phosphorylation of IRF3, a key transcription factor involved in interferon (IFN) synthesis, one essential element of the innate immune response. RIG-I remains in an autoinhibited state in the absence of dsRNA, through an internal repressor domain (RD) that binds within both its CARD and its RNA helicase domains and therefore acts in cis to control its multimerization and interaction with IPS-1. Ectopic expression of the RD prevents signaling and increases cell permissiveness to viruses, including hepatitis C virus. LGP2, which is another DExD/H RNA helicase of the RIG-I and MDA5 family and which is devoid of CARD domain, negatively controls IFN induction at different levels: by sequestering dsRNA, by blocking RIG-I’s multimerization in trans through a domain analogous to the RIG-I RD, and by competing with the protein kinase IKK{varepsilon} for a common interaction site on IPS-1. The ability of RIG-I and LGP2 to exert such a feedback control at the earliest steps of IFN synthesis allows the cells to exert a tight regulation of the induction of the innate immune response.

*Corresponding author: Address, Unit Hepacivirus, Department Virology, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France; telephone, (33) 1 45 68 87 77; fax, (33) 1 40 61 30 12; e-mail, emeurs{at}pasteur.fr

Citation: D. Vitour, E. F. Meurs, Regulation of Interferon Production by RIG-I and LGP2: A Lesson in Self-Control. Sci. STKE 2007, pe20 (2007).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Protective Role of LGP2 in Influenza Virus Pathogenesis.
M. Si-Tahar, F. Blanc, L. Furio, D. Chopy, V. Balloy, M. Lafon, M. Chignard, L. Fiette, F. Langa, P. Charneau, et al. (2014)
The Journal of Infectious Disease
   Abstract »    Full Text »    PDF »
Polo-like Kinase 1 (PLK1) Regulates Interferon (IFN) Induction by MAVS.
D. Vitour, S. Dabo, M. Ahmadi Pour, M. Vilasco, P.-O. Vidalain, Y. Jacob, M. Mezel-Lemoine, S. Paz, M. Arguello, R. Lin, et al. (2009)
J. Biol. Chem. 284, 21797-21809
   Abstract »    Full Text »    PDF »
The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA.
D. A. Pippig, J. C. Hellmuth, S. Cui, A. Kirchhofer, K. Lammens, A. Lammens, A. Schmidt, S. Rothenfusser, and K.-P. Hopfner (2009)
Nucleic Acids Res. 37, 2014-2025
   Abstract »    Full Text »    PDF »
Structure and Function of LGP2, a DEX(D/H) Helicase That Regulates the Innate Immunity Response.
A. Murali, X. Li, C. T. Ranjith-Kumar, K. Bhardwaj, A. Holzenburg, P. Li, and C. C. Kao (2008)
J. Biol. Chem. 283, 15825-15833
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882