Synergistic Interaction of Interferon- and Interferon- in Coxsackievirus B3-Infected Carrier Cultures of Human Myocardial Fibroblasts

Abstract

The antiviral effects of human interferon-β (IFN-β) and human recombinant interferon-γ (rIFN-γ) were studied in persistently coxsackievirus B3-infected carrier cultures of human myocardial fibroblasts over a period of 21 days. Synergism was observed with concentrations as low as 30 IU of IFN-β plus 10 IU of rIFN-γ/mL, reducing mean viral titers from 6.0 × 10⁷ to 1.3 × 10⁴ pfu/mL and number of infected cells from 14.4% to 0.1% as determined by quantitative in situ hybridization. Higher concentrations of IFNs (both ⩾ 30 IU/mL) were associated with transient antagonism followed by antiviral synergism. With 100 IU of IFN-β plus 30 IU of rIFN-γ/mL, elimination of infectious virus was consistently achieved and sustained for 6 weeks after cessation of IFN application, whereas at least threefold higher concentrations were required with single drugs. In summary, our data support a concept of low-dose IFN combination schedules that might become useful in the treatment of enteroviral heart disease.