Interferon regulatory factor 3 is required for viral induction of beta interferon in primary cardiac myocyte cultures.
Viral myocarditis affects an estimated 5 to 20% of the human population. The antiviral cytokine beta interferon (IFN-beta) is critical for protection against viral myocarditis in mice. That is, nonmyocarditic reoviruses induce myocarditis in mice that lack IFN-alpha/beta, and nonmyocarditic reoviruses both induce more IFN-beta and are more sensitive to the antiviral effects of IFN-beta than myocarditic reoviruses in primary cardiac myocyte cultures. Induction of IFN-beta in certain cell types involves viral activation of the transcription factor interferon regulatory factor 3 (IRF-3). To address whether IRF-3 can induce IFN-beta in cardiac myocytes, primary cardiac myocyte cultures and control L929 cells were transfected with a plasmid constitutively expressing IRF-3. Overexpression of IRF-3 resulted in induction of IFN-beta in the absence of viral infection in both cell types. To address whether IRF-3 is required for viral induction of IFN-beta, cell cultures were transfected with a plasmid constitutively expressing a dominant negative IRF-3 protein. The dominant negative IRF-3 reduced reovirus induction of IFN-beta in control L929 cells and completely eliminated induction in primary cardiac myocyte cultures. This provides the first identification of a cardiac cellular factor required for viral induction of IFN-beta and the first report of any cell type requiring IRF-3 for this response.
Noah
D L
DL
Department of Microbiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.
Blum
M A
MA
Sherry
B
B
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D050838:Interferon Regulatory Factor-3; D016899:Interferon-beta / Q000096:biosynthesis* / Q000276:immunology; D008156:Luciferases / Q000235:genetics; D012089:Mammalian orthoreovirus 3 / Q000276:immunology* / Q000502:physiology; D051379:Mice; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010957:Plasmids; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D014157:Transcription Factors; D016899:Interferon-beta; D008156:Luciferases