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

Carolina Scagnolari, Simona Trombetti, Alessia Alberelli, Simona Cicetti, Daniela Bellarosa, Roberta Longo, Alberto Spanò, Elisabetta Riva, Massimo Clementi, Guido Antonelli
Intervirology 2007, 50 (2): 156-60
Interferon (IFN)-alpha, -beta and -gamma 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-alpha or -beta) and IFN-gamma 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-gamma parallels the marked increase in 2'-5'-oligoadenylate synthetase and p56 mRNAs following exposure in Vero cells to either IFN-alpha or -beta and IFN-gamma 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.

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