IFN-alpha expression and antiviral effects are subtype and cell type specific in the cardiac response to viral...

The interferon-beta (IFN-beta) response is critical for protection against viral myocarditis in several mouse models, and IFN-alpha or -beta treatment is beneficial against human viral myocarditis. The IFN-beta response in cardiac myocytes and cardiac fibroblasts forms an integrated network for organ protection; however, the different IFN-alpha subtypes have not been studied in cardiac cells. We developed a quantitative RT-PCR assay that distinguishes between 13 highly conserved IFN-alpha subtypes and found that reovirus T3D induces five IFN-alpha subtypes in primary cardiac myocyte and fibroblast cultures: IFN-alpha1, -alpha2, -alpha4, -alpha5, and -alpha8/6. Murine IFN-alpha1, -alpha2, -alpha4, or -alpha5 treatment induced IRF7 and ISG56 and inhibited reovirus T3D replication in both cell types. This first investigation of IFN-alpha subtypes in cardiac cells for any virus demonstrates that IFN-alpha is induced in cardiac cells, that it is both subtype and cell type specific, and that it is likely important in the antiviral cardiac response.