Interaction of the SARS-Coronavirus with the interferon system

α / β干扰素（ifn）是具有抗病毒活性的强效细胞因子。它们由病毒感染诱导并触发抗病毒蛋白的表达。为了对抗这种情况，病毒进化出了所谓的干扰素拮抗剂，它可以干扰干扰素诱导、干扰素信号传导或干扰素效应蛋白的作用。我们发现SARS-CoV被IFN- β和一种新的IFN， IFN-omega强烈抑制。相比之下，ifn - α的效果较差。此外，研究发现感染SARS-CoV的细胞不能合成IFN，这表明SARS-CoV至少编码一种具有IFN拮抗活性的因子。德国团队提出的研究将旨在(i)鉴定宿主编码的ifn诱导的蛋白质，这些蛋白质负责对SARS-CoV产生抗病毒作用，（ii）筛选SARS-CoV基因组中具有抗ifn活性的蛋白质，以及（iii）表征ifn拮抗机制。中国研究小组将研究从中国患者身上分离的病毒在抗干扰素基因上的潜在差异。这些ifn拮抗基因的活性将在中国病毒分离株之间进行比较，并与细胞培养适应的病毒分离株进行比较。此外，将测量患者材料中不同IFN的水平，并测试是否与疾病进展和某些IFN拮抗剂序列相关。IFN-omega已获得中国食品药品监督管理局（FDA）许可，用于预防SARS的鼻内喷雾剂。关于抗病毒效果和IFN-omega、- β或- α in不同诱导的IFN效应的比较研究将有助于阐明哪种抗病毒蛋白最有效地抑制SARS-CoV。这些研究可能有助于鉴定影响SARS-CoV感染结果的毒力机制和宿主防御因子。这些研究的长期益处可能是抗病毒治疗的改进和SARS-CoV疫苗的合理设计。

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.