biostudies-literatureKimura TNIAID NIH HHSNCI NIH HHSe1007674https://www.ebi.ac.uk/biostudies/studies/S-EPMC6453442biostudies-literatureUnknown15(4)Viral myocarditis is a serious disease, commonly caused by type B coxsackieviruses (CVB). Here we show that innate immune protection against CVB3 myocarditis requires the IFIT (IFN-induced with tetratricopeptide) locus, which acts in a biphasic manner. Using IFIT locus knockout (IFITKO) cardiomyocytes we show that, in the absence of the IFIT locus, viral replication is dramatically increased, indicating that constitutive IFIT expression suppresses CVB replication in this cell type. IFNβ pre-treatment strongly suppresses CVB3 replication in wild type (wt) cardiomyocytes, but not in IFITKO cardiomyocytes, indicating that other interferon-stimulated genes (ISGs) cannot compensate for the loss of IFITs in this cell type. Thus, in isolated wt cardiomyocytes, the anti-CVB3 activity of IFITs is bPLoS pathogensBiphasic and cardiomyocyte-specific IFIT activity protects cardiomyocytes from enteroviral infection.PMC6453442R01 AI110621R01 AI114615R01 CA068782P01 CA062220Flynn CTSen GCKimura TAlirezaei MWhitton JLfalseBiphasic and cardiomyocyte-specific IFIT activity protects cardiomyocytes from enteroviral infection.Viral myocarditis is a serious disease, commonly caused by type B coxsackieviruses (CVB). Here we show that innate immune protection against CVB3 myocarditis requires the IFIT (IFN-induced with tetratricopeptide) locus, which acts in a biphasic manner. Using IFIT locus knockout (IFITKO) cardiomyocytes we show that, in the absence of the IFIT locus, viral replication is dramatically increased, indicating that constitutive IFIT expression suppresses CVB replication in this cell type. IFNβ pre-treatment strongly suppresses CVB3 replication in wild type (wt) cardiomyocytes, but not in IFITKO cardiomyocytes, indicating that other interferon-stimulated genes (ISGs) cannot compensate for the loss of IFITs in this cell type. Thus, in isolated wt cardiomyocytes, the anti-CVB3 activity of IFITs is b2019-01-01T00:00:00Z2019 Apr2025-04-04T13:25:22.771Z2019-06-06T21:07:26ZS-EPMC64534423095886710.1371/journal.ppat.1007674