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Journal of Virology, December 2006, p. 12332-12342, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01325-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

RNA- and Virus-Independent Inhibition of Antiviral Signaling by RNA Helicase LGP2{triangledown}

Akihiko Komuro1,2 and Curt M. Horvath1,2*

Department of Medicine and Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208,1 Department of Medicine, Evanston Northwestern Healthcare, Evanston, Illinois 602082

Received 23 June 2006/ Accepted 25 September 2006

Antiviral innate immune responses can be triggered by accumulation of intracellular nucleic acids resulting from virus infections. Double-stranded RNA (dsRNA) can be detected by the cytoplasmic RNA helicase proteins RIG-I and MDA5, two proteins that share sequence similarities within a caspase recruitment domain (CARD) and a DExD/H box RNA helicase domain. These proteins are considered dsRNA sensors and are thought to transmit the signal to the mitochondrial adapter, IPS-1 (also known as MAVS, VISA, or CARDIF) via CARD interactions. IPS-1 coordinates the activity of protein kinases that activate transcription factors needed to induce beta interferon (IFN-ß) gene transcription. Another helicase protein, LGP2, lacks the CARD region and does not activate IFN-ß gene expression. LGP2 mRNA is induced by interferon, dsRNA treatments, or Sendai virus infection and acts as a feedback inhibitor for antiviral signaling. Results indicate that LGP2 can inhibit antiviral signaling independently of dsRNA or virus infection intermediates by engaging in a protein complex with IPS-1. Experiments suggest that LGP2 can compete with the kinase IKKi (also known as IKK{varepsilon}) for a common interaction site on IPS-1. These results provide the first demonstration of protein interaction as an element of negative-feedback regulation of intracellular antiviral signaling by LGP2.

* Corresponding author. Mailing address: Pancoe-ENH Research Pavilion, Northwestern University, 2200 Campus Drive, Evanston, IL 60208. Phone: (847) 491-5530. Fax: (847) 491-4400. E-mail: Horvath{at}northwestern.edu.

{triangledown} Published ahead of print on 4 October 2006.

Journal of Virology, December 2006, p. 12332-12342, Vol. 80, No. 24
0022-538X/06/$08.00+0     doi:10.1128/JVI.01325-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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