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Journal of Virology, April 2002, p. 3659-3669, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3659-3669.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Recognition of the Measles Virus Nucleocapsid as a Mechanism of IRF-3 Activation

Benjamin R. tenOever,1,2 Marc J. Servant,1,2 Nathalie Grandvaux,1,2 Rongtuan Lin,1,2 and John Hiscott1,2,3*

Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research,1 Departments of Microbiology and Immunobiology,3 Medicine, McGill University, Montreal, Quebec, Canada H3T 1E22

Received 14 August 2001/ Accepted 16 January 2002

The mechanisms of cellular recognition for virus infection remain poorly understood despite the wealth of information regarding the signaling events and transcriptional responses that ensue. Host cells respond to viral infection through the activation of multiple signaling cascades, including the activation of NF-{kappa}B, c-Jun/ATF-2 (AP-1), and the interferon regulatory factors (IRFs). Although viral products such as double-stranded RNA (dsRNA) and the processes of viral binding and fusion have been implicated in the activation of NF-{kappa}B and AP-1, the mechanism(s) of IRF-1, IRF-3, and IRF-7 activation has yet to be fully elucidated. Using recombinant measles virus (MeV) constructs, we now demonstrate that phosphorylation-dependent IRF-3 activation represents a novel cellular detection system that recognizes the MeV nucleocapsid structure. At low multiplicities of infection, IRF-3 activation is dependent on viral transcription, since UV cross-linking and a deficient MeV containing a truncated polymerase L gene failed to induce IRF-3 phosphorylation. Expression of the MeV nucleocapsid (N) protein, without the requirement for any additional viral proteins or the generation of dsRNA, was sufficient for IRF-3 activation. In addition, the nucleocapsid protein was found to associate with both IRF-3 and the IRF-3 virus-activated kinase, suggesting that it may aid in the colocalization of the kinase and the substrate. Altogether, this study suggests that IRF-3 recognizes nucleocapsid structures during the course of an MeV infection and triggers the induction of interferon production.

* Coresponding author. Mailing address: Lady Davis Institute for Medical Research, 3755 Cote St. Catherine, Montreal, Quebec H3T 1E2, Canada. Phone: (514) 340-8222. Fax: (514) 340-7576. E-mail: jhisco{at}po-box.mcgill.ca.

Journal of Virology, April 2002, p. 3659-3669, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3659-3669.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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