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

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-V^minus infection, in contrast, behaves mostly like wt SeV and counteracts the effects of transfected poly(I-C) or _pppRNAs.

Published ahead of print on 5 September 2007.