Severe acute respiratory syndrome coronavirus elicits a weak interferon response compared to traditional interferon-inducing viruses.

The aim of the present study is to investigate changes of interferon (IFN) production occurring over the first 48 h after infection of peripheral blood mononuclear cells (PBMCs) with severe acute respiratory syndrome (SARS) coronavirus (CoV) and to compare these changes to those induced by well-established IFN-inducing viruses, such as vesicular stomatitis (VSV) and Newcastle viruses (NDV). Experiments have been carried out using PBMCs of 10 different healthy donors. The results showed that the antiviral activity of IFN contained in the supernatant of SARS-CoV-infected PBMCs was lower than those induced by VSV and NDV. Consequently, SARS-CoV induces a lower synthesis of IFN-alpha, -beta and -gamma compared to VSV and NDV. Characterization of the profile of IFN-alpha subtypes genes expression in SARS-CoV-infected PBMCs demonstrated that the level of IFN-alpha2 and -6 subtypes were higher compared to other IFN-alpha subtypes namely, IFN-alpha5, -8, -10, -13/1, -17, and -21. In conclusion, SARS-CoV induces IFNs to a less extent compared to VSV and NDV, thus suggesting that the IFN system does play a limited role in early host defense against SARS-CoV infection.

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.

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.