Cbl-b缺失促进pDC干扰素表达进而抑制呼吸道合胞病毒在巨噬细胞中的扩增研究

RSV是临床儿童感染导致肺炎和细支气管炎的重要致病原。迄今为止，尚无有效的预防疫苗和治疗药物。干扰素在病毒感染中发挥重要作用。但在RSV感染过程中IFN产生的机制还不甚清楚。我们预实验结果提示，E3泛素连接酶Cbl-b敲除后，RSV感染模型小鼠肺部炎症显著减轻。通过细胞生物学和分子生物学方法进一步研究发现：巨噬细胞是RSV感染的主要细胞，而pDC是I型和II型IFN产生的主要细胞。Cbl-b敲除后pDC产生更多的IFN，这些IFN最终通过作用于巨噬细胞，从而抑制RSV在巨噬细胞内的扩增。同时我们发现Cbl-b可能通过降解IRF3来干扰IFN的产生。本课题拟在已有的研究基础上深入探讨Cbl-b对RSV感染过程中IFN表达调控的分子机制，为RSV感染诱导的IFN分子机制提供新的解释，为RSV临床治疗提供新的思路。

RSV is an important cause of pneumonia and bronchiolitis in children. So far, there is no effective preventive vaccine and treatment drugs for RSV infection. Interferon plays an important role in virus infection. However, the mechanism of IFN production in RSV infection is not very clear. Our preliminary results suggested that the lung inflammation of RSV infected mice was significantly reduced in the E3 ubiquitin ligase Cbl-b knockout mice. By some cell biology and molecular biology experiments, we found that macrophage is the main cells of RSV infection, and PDC is the main source of type I and type II IFN production. After Cbl-b knockout, PDC produced more IFNs, which eventually inhibited the expansion of RSV in macrophages. At the same time, we found that Cbl-b may interfere with IFN production by degrading IRF3. Based on the existing research, we intends to further explore the molecular mechanism of Cbl-b on the regulation of IFN expression in RSV infection in this project, provide a new explanation for the molecular mechanism of IFN induced by RSV infection, and provide a new idea for the clinical treatment of RSV.