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Journal of Virology, November 2007, p. 12227-12237, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.01300-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Activation of the Beta Interferon Promoter by Unnatural Sendai Virus Infection Requires RIG-I and Is Inhibited by Viral C Proteins{triangledown}

Laura Strähle, Jean-Baptiste Marq, Albert Brini, Stéphane Hausmann, Daniel Kolakofsky,* and Dominique Garcin

Department of Microbiology and Molecular Medicine, University of Geneva School of Medicine, 11 Ave. de Champel, CH1211 Geneva, Switzerland

Received 14 June 2007/ Accepted 27 August 2007

As infection with wild-type (wt) Sendai virus (SeV) normally activates beta interferon (IFN-ß) very poorly, two unnatural SeV infections were used to study virus-induced IFN-ß activation in mouse embryonic fibroblasts: (i) SeV-DI-H4, which is composed mostly of small, copyback defective interfering (DI) genomes and whose infection overproduces short 5'-triphosphorylated trailer RNAs (pppRNAs) and underproduces viral V and C proteins, and (ii) SeV-GFP(+/–), a coinfection that produces wt amounts of viral gene products but that also produces both green fluorescent protein (GFP) mRNA and its complement, which can form double-stranded RNA (dsRNA) with capped 5' ends. We found that (i) virus-induced signaling to IFN-ß depended predominantly on RIG-I (as opposed to mda-5) for both SeV infections, i.e., that RIG-I senses both pppRNAs and dsRNA without 5'-triphosphorylated ends, and (ii) it is the viral C protein (as opposed to V) that is primarily responsible for countering RIG-I-dependent signaling to IFN-ß. Nondefective SeV that cannot specifically express C proteins not only cannot prevent the effects of transfected poly(I-C) or pppRNAs on IFN-ß activation but also synergistically enhances these effects. SeV-Vminus infection, in contrast, behaves mostly like wt SeV and counteracts the effects of transfected poly(I-C) or pppRNAs.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Medicine, University of Geneva School of Medicine, 11 Ave. de Champel, CH1211 Geneva, Switzerland. Phone: 41-223795657. Fax: 41-223795702. E-mail: Daniel.Kolakofsky{at}medecine.unige.ch

{triangledown} Published ahead of print on 5 September 2007.

Journal of Virology, November 2007, p. 12227-12237, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.01300-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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