Virale Zweckentfremdung des Proteins DDB1 als Evasionsstrategie gegen angeborene Immunität (A07)

A7项目将分析慢性病毒如何抵消干扰素反应。慢性病毒通常利用DDB1和含cullin的泛素连接酶途径降解IFN信号通路分子或IFN诱导的限制性因子。HIV （vpx）和HBV （HBx）蛋白也利用这一途径，我们将对其进行更详细的分析。最重要的是，A7项目的pi使用Cullin酶活性的小分子抑制剂，对几种病毒显示出很高的抗病毒活性。它对FV、HIV、HTLV、HCV和HBV的治疗效果将在体外进行测试，如果可能的话，也将在体内进行测试。此外，IFNγ的抗病毒特征将在这些研究中进行分析。该小组定义了IFNγ诱导和抑制蛋白的模式，从而可以详细表征它们对逆转录病毒的抗病毒活性。

Project A7 will analyze how chronic viruses counteract IFN responses. Chronic viruses often utilize the DDB1 and Cullin-containing ubiquitin ligase pathway to degrade molecules of the IFN signaling pathway or IFN-induced restriction factors. Also HIV (vpx) and HBV (HBx) proteins exploit this pathway, which will be analyzed in greater detail. Most importantly, the PIs of project A7 use a small molecule inhibitor of the Cullin enzymatic activity that shows high antiviral activity against several viruses. Its therapeutic effect against FV, HIV, HTLV, HCV and HBV will be tested in vitro and if possible in vivo. Furthermore, the antiviral profile of IFNγ will be analyzed in these studies. The group defined a pattern of IFNγ induced and repressed proteins that allows the detailed characterization of their antiviral activity against retroviruses.