Type I interferons are essential mediators of apoptotic death in virally infected cells

Abstract

BACKGROUND: The interferons (IFNs) have been extensively studied in the context of host defence against viral infection. In the established model of IFN action, virally infected cells secrete type I IFNs (IFN-alpha/beta) which induce an antiviral state in uninfected cells. However, it is not clear how IFNs function on the infected cells. It has been reported that cells infected by some viruses die by apoptosis. RESULTS: In the present study, we found that three types of viruses commonly induce apoptosis in primary cell cultures. Importantly, we observed that virus-induced apoptosis was inhibited by anti-IFN-alpha/beta antibodies, and in cells lacking either the type I IFN receptor 1 (IFNAR1) or its downstream mediator, Stat1 (Signal transducer and activator of transcription 1). IFN-alpha treatment by itself did not induce apoptosis unless it was combined with transfection by double-stranded RNA (dsRNA), which is normally generated during the course of viral infection. CONCLUSION: These results indicate a novel antiviral function of the type I IFNs, i.e. the selective induction of apoptosis in virally infected cells. In effect, these IFNs have a bifunctional role in limiting the spread of virus; eliciting an antiviral state in uninfected cells while promoting apoptosis in infected cells. Our results may help explain why IFNs are sometimes useful in the treatment of viral diseases and will provide further insight into the mechanisms of virus-induced pathogenesis.