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

The interferon-β (IFN-β) response is critical for protection against viral myocarditis in several mouse models, and IFN-α or -β treatment is beneficial against human viral myocarditis. The IFN-β response in cardiac myocytes and cardiac fibroblasts forms an integrated network for organ protection; however, the different IFN-α subtypes have not been studied in cardiac cells. We developed a quantitative RT-PCR assay that distinguishes between 13 highly conserved IFN-α subtypes and found that reovirus T3D induces five IFN-α subtypes in primary cardiac myocyte and fibroblast cultures: IFN-α1, -α2, -α4, -α5, and -α8/6. Murine IFN-α1, -α2, -α4, or -α5 treatment induced IRF7 and ISG56 and inhibited reovirus T3D replication in both cell types. This first investigation of IFN-α subtypes in cardiac cells for any virus demonstrates that IFN-α 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.