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-ฮฑ, -ฮฒ and -ฮณ compared to VSV and NDV. Characterization of the profile of IFN-ฮฑ subtypes genes expression in SARS-CoV-infected PBMCs demonstrated that the level of IFN-ฮฑ2 and -6 subtypes were higher compared to other IFN-ฮฑ subtypes namely, IFN-ฮฑ5, -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. Copyright ยฉ 2008 S. Karger AG.