Interferon-γ-Induced Activation of Nitric Oxide-Mediated Antiviral Activity of Macrophages Caused by a Recombinant Coxsackievirus B3

Cardiovascular disease is one of the major causes of human death and has been linked to many different risks including viral infections. Coxsackievirus B3 (CVB3) is one of the most important pathogens responsible for virus-induced myocarditis. Cytokines are normally involved in the control of CVB3 replication and pathogenesis. Among them, interferon-γ (IFN-γ) in particular is highly protective against CVB3. A novel strategy to circumvent virus-caused heart disease is based on the development of cytokine-expressing recombinant virus vectors. Using in vitro co-culture experiments, the release of IFN-γ by the recombinant virus variant CVB3/IFN-γ activates the expression of the inducible nitric oxide synthase (iNOS) in CVB3 non-susceptible murine macrophages and the release of nitric oxide (NO), which reduce coxsackieviral replication directly. In addition, the expression of IFN-γ by CVB3/IFN-γ contributes to protect mice from lethal infections by iNOS induction in murine peritoneal macrophages, viral load re...