Recombinant Interferons β and γ Have a Higher Antiviral Activity than Interferon-α in Coxsackievirus B3-Infected Carrier State Cultures of Human Myocardial Fibroblasts

Abstract

We compared the antiviral activities of three recombinant human interferons (IFN-α2a, IFN-β, and IFN-γ) in cultured human myocardial fibroblasts to select a candidate for trial in heart disease induced by cardiotropic enterovirus, e.g., coxsackievirus B3 (CVB3). Cells were exposed to CVB3, and after 7 days, when a persistent infection had developed, IFN was added. Virus yields were measured on alternate days for the next 7 or 16 days, and IFN activity was assessed as the percentage reduction in yield. IFN-γ and IFN-β were both highly active and reduced virus yields by 2 log (EC₉₉) at concentrations of 23.4 IU/ml (SD = 8.6) and 10.1 IU/ml (SD = 3.2), respectively; with 250 IU/ml of either IFN, no infectious virus was formed. Unexpectedly, IFN-α2a (EC₉₉ > 1250 IU/ml) was at least 120 times less active than IFN-β; after use for 8 days or more, the minor effects it produced were no longer related to the concentration applied. Despite the pharmacokinetic advantages of IFN-α2a, our data suggest that IFN-β should in preference be evaluated in the clinic.