The Synergistic Interaction of Interferon Types I and II Leads to Marked Reduction in Severe Acute Respiratory Syndrome-Associated Coronavirus Replication and Increase in the Expression of mRNAs for Interferon-Induced Proteins

Scagnolari, Carolina; Trombetti, Simona; Alberelli, Alessia; Cicetti, Simona; Bellarosa, Daniela; Longo, Roberta; Spanò, Alberto; Riva, Elisabetta; Clementi, Massimo; Antonelli, Guido

Interferon (IFN)-α, -β and -γ have been shown to be only marginally effective against severe acute respiratory syndrome coronavirus (SARS-CoV) replication in Vero cell lines. We investigated the combination of type I IFNs (IFN-α or -β) and IFN-γ for antiviral activity and found that such combinations synergistically inhibited SARS-CoV replication in Vero cells, using yield reduction assay and the isobologram and combination index methods of Chou and Talalay for evaluation. The highly synergistic anti-SARS-CoV action of type I IFNs and IFN-γ parallels the marked increase in 2′-5′-oligoadenylate synthetase and p56 mRNAs following exposure in Vero cells to either IFN-α or -β and IFN-γ compared with the transcriptional levels obtained after stimulation with either IFN alone. These results demonstrate that SARS-CoV, although only moderately sensitive to the antiviral action of the individual types of IFN, is highly sensitive to a combination of type I and II IFNs, which suggests that such combinations may have potential in the treatment of SARS-CoV infections.