Activation of the beta interferon promoter by unnatural Sendai virus infection requires RIG-I and is inhibited by viral C proteins.
As infection with wild-type (wt) Sendai virus (SeV) normally activates beta interferon (IFN-beta) very poorly, two unnatural SeV infections were used to study virus-induced IFN-beta 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-beta 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-beta. Nondefective SeV that cannot specifically express C proteins not only cannot prevent the effects of transfected poly(I-C) or (ppp)RNAs on IFN-beta 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 (ppp)RNAs.
Strähle
Laura
L
Department of Microbiology and Molecular Medicine, University of Geneva School of Medicine, 11 Ave de Champel, CH1211, Geneva, Switzerland.
Marq
Jean-Baptiste
JB
Brini
Albert
A
Hausmann
Stéphane
S
Kolakofsky
Daniel
D
Garcin
Dominique
D
D000818:Animals; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D000072640:Interferon-Induced Helicase, IFIH1; D016899:Interferon-beta / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D012313:RNA / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology; D012367:RNA, Viral / Q000378:metabolism; D029082:Sendai virus / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*