SNX8正调控DNA病毒诱导的天然免疫反应

How the host initiates efficient innate immune response after viral infection is a key question in the past years. In our preliminary studies, we found that SNX8 is essential for DNA virus-triggered induction of downstream antiviral genes. We also found SNX8 interacted with MITA in overexpression systems. In addition, the translocation of MITA from ER to peri¬nuclear microsomes induced by HSV-1 infection was inhibited and the expression of MITA was markedly down-regulated in SNX8-deficient MLFs in comparison with wild-type MLFs. Based on these results, we hypothesize that SNX8 regulates the trafficking and stability of MITA to facilitate innate antiviral response to DNA virus. This project will further investigate the molecular mechanisms on how SNX8 regulates the function of MITA and the roles of SNX8 in host defense against viral infection in vivo.

病毒感染后，宿主如何启动有效的抗病毒天然免疫以清除病毒是生物医学的一个热点问题。在前期工作中，我们发现SNX8在DNA病毒感染诱导下游抗病毒基因表达中发挥重要作用。并且我们发现，在过量表达体系中，SNX8能够特异性地与MITA相互作用。此外，初步研究发现，在SNX8表达缺失的MLF细胞中，HSV-1诱导的MITA从ER向核周微小体的迁移明显减少，并且MITA的蛋白水平也明显降低。根据这些前期结果，我们提出的工作假说是SNX8很可能调控了抗DNA病毒天然免疫信号通路中关键接头蛋白MITA的转运和稳定性。本项目将进一步研究SNX8调节MITA的具体分子机制以及SNX8在机体抗DNA病毒天然免疫应答中的生理功能。

病毒感染通过激活转录因子NF-kB和IRF3诱导I型干扰素和促炎症因子的表达。本项目在我们前期工作的基础上，进一步探究了SNX8等蛋白在抗病毒天然免疫反应中的功能和调控机制。在项目执行期间，我们鉴定了多个参与调控抗病毒天然免疫的信号蛋白（如SNX8，ZCCHC3和ZFYVE1）。发表了6篇论文，包括1篇Cell Research，2篇CMI，1篇PLoS Pathogens，1篇JMCB和1篇Advances in Immunology。