Interaction of the SARS-Coronavirus with the interferon system

• Applicant: Professor Dr. Friedemann Weber
• Subject Area: Virology
• Term: from 2004 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5437828

Alpha/beta interferons (IFNs) are potent cytokines with antiviral activity. They are induced by virus infection and trigger the expression of antiviral proteins. To counteract this, viruses have evolved so-called IFN antagonists, which interfere with either IFN induction, IFN signaling, or the action of IFN effector proteins. We found that SARS-CoV is strongly inhibited by IFN-beta and by a novel IFN, IFN-omega. IFN-alpha, by contrast, was less effective. Furthermore, it was found that cells infected with SARS-CoV are unable to synthesize IFN, indicating that SARS-CoV encodes at least one factor with IFN-antagonistic activity. The proposed studies of the German team will be aimed at (i) identifying the host-encoded IFN-induced proteins which are responsible for the antiviral effect against SARS-CoV, (ii) screening the SARS-CoV genome for proteins with anti-IFN activity, and (iii) characterizing the IFN-antagonistic mechanism. The Chinese team will investigate virus isolates from Chinese patients for potential differences in the anti-IFN genes. The activity of those IFN-antagonistic genes of Chinese virus isolates will be compared to each other and to cell culture adapted virus isolates. Furthermore, levels of different IFNs will be measured in patients' material and tested whether there is a correlation with disease progression and with certain IFN antagonist sequences. IFN-omega is licensed by the Chinese FDA for prevention of SARS by intranasal spray application. Comparative studies concerning the antiviral effects and the differently induced IFN effectors of IFN-omega, -beta, or -alpha in will help to clarify which antiviral protein most potently inhibits SARS-CoV. These studies may lead to the identification of virulence mechanisms and host defense factors which influence the outcome of infection with SARS-CoV. Long-term benefits of those studies could be the improvement of antiviral therapy and the rational design of SARS-CoV vaccines.

• DFG Programme: Research Grants
• International Connection: China
• Participating Persons: Dr. Wei Chen; Dr. Yu-Mei Wen; Dr. Zhenghong Yuan