Interaction of the SARS-Coronavirus with the interferon system

SARS冠状病毒与干扰素系统的相互作用

• 批准号: 5437828
• 负责人: Professor Dr. Friedemann Weber
• 金额: --
• 依托单位: Institut für Virologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2007-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5437828?language=en
• 关键词: Interaction; SARS; Coronavirus; interferon; system

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.

α/β 干扰素 (IFN) 是具有抗病毒活性的有效细胞因子。它们由病毒感染诱导并触发抗病毒蛋白的表达。为了解决这个问题，病毒进化出了所谓的干扰素拮抗剂，它干扰干扰素诱导、干扰素信号传导或干扰素效应蛋白的作用。我们发现 SARS-CoV 受到 IFN-beta 和一种新型 IFN IFN-omega 的强烈抑制。相比之下，IFN-α 的效果较差。此外，还发现感染SARS-CoV的细胞无法合成IFN，表明SARS-CoV编码至少一种具有IFN拮抗活性的因子。德国团队拟议的研究旨在（i）鉴定宿主编码的干扰素诱导蛋白，这些蛋白负责对抗 SARS-CoV 的抗病毒作用，（ii）筛选 SARS-CoV 基因组中具有抗干扰素活性的蛋白质，以及（iii）表征干扰素拮抗机制。中国团队将调查从中国患者身上分离出的病毒，以了解抗干扰素基因的潜在差异。中国病毒分离株的那些 IFN 拮抗基因的活性将相互比较，并与适应细胞培养的病毒分离株进行比较。此外，将测量患者材料中不同干扰素的水平，并测试是否与疾病进展和某些干扰素拮抗剂序列相关。 IFN-omega已获得中国FDA许可，可通过鼻内喷雾预防SARS。关于 IFN-omega、-β 或 -α 的抗病毒作用和不同诱导的 IFN 效应子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确定影响 SARS-CoV 感染结果的毒力机制和宿主防御因素。这些研究的长期好处可能是抗病毒治疗的改进和 SARS-CoV 疫苗的合理设计。