Viral induction of Zac1b through TLR3- and IRF3-dependent pathways.
Zinc finger protein regulator of apoptosis and cell cycle arrest (Zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways. In spite of the important potential functions attributed to Zac1, little is known of its physiological regulation and biological function. We discovered that variant Zac1b was expressed in murine embryonic fibroblasts (MEFs) treated with polyriboinosinic polyribocytidylic acid [poly(I:C)], a synthetic double-stranded RNA. This regulation occurred mainly through Toll-Like Receptor 3 (TLR3)- and Interferon Regulatory Factor 3 (IRF3)-dependent pathways. As TLR3 and IRF3 are central activators of antiviral immunity, we hypothesized that Zac1 may be implicated in antiviral responses. In line with this notion, we observed that Zac1b was expressed in MEFs infected with Encephalomyocarditis virus (EMCV). We also observed that Zac1-deficient MEFs were less sensitive to EMCV-induced cell death than wild-type MEFs. However, Zac1 gene inactivation had no effect on the survival of mice infected with EMCV. In conclusion, this study describes for the first time a transcriptional regulation of Zac1b, induced by synthetic dsRNA and RNA viruses, the functional significance of which remains to be further investigated.
Warzée
Barbara
B
Laboratory of Cellular and Molecular Physiology, GIGA-Research, University of Liege, Liege, Belgium.
Mesnil
Claire
C
Hober
Didier
D
Caloone
Delphine
D
Pirottin
Dimitri
D
Garigliany
Mutien-Marie
MM
Desmecht
Daniel
D
Drion
Pierre-Vincent
PV
Journot
Laurent
L
Lekeux
Pierre
P
Bureau
Fabrice
F
Desmet
Christophe J
CJ
D000818:Animals; D018188:Cardiovirus Infections / Q000276:immunology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D004686:Encephalomyocarditis virus; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D016147:Genes, Tumor Suppressor; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D050838:Interferon Regulatory Factor-3 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012328:RNA Viruses / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014162:Transfection
D018797:Cell Cycle Proteins; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; C498423:Plagl1 protein, mouse; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D014157:Transcription Factors