LGP2抗口蹄疫病毒感染天然免疫信号分子机制

LGP2在抗病毒天然免疫中发挥着非常重要的作用，但其抗口蹄疫病毒（FMDV）感染的天然免疫机制仍不清楚。本项目前期研究表明，过表达LGP2能够显著抑制FMDV复制，而FMDV感染也能够诱导LGP2 mRNA上调表达，进一步鉴定出FMDV的2B和3C蛋白抑制或降解LGP2蛋白表达。为进一步阐明LGP2抗FMDV感染的天然免疫机制，本研究首先从LGP2抑制FMDV复制入手，确定LGP2发挥抗FMDV感染的功能域和位点，并进一步鉴定出LGP2抗FMDV作用的下游效应分子及其调控信号通路，确定其发挥功能的具体分子机制。同时，寻找能与LGP2相互作用的病毒蛋白并鉴定作用位点，鉴定2B及3C蛋白裂解或降解LGP2的分子机制。最后，利用反向遗传操作系统构建关键位点突变重组病毒进行进一步验证。本研究为阐明LGP2抗FMDV感染的天然免疫机制奠定基础。

The laboratory of genetics and physiology 2 (LGP2) is widely involved in viral RNA recognition and innate immune regulation during virus infection; however, the involved mechanism during FMDV infection remains unclear. Our previous study showed that FMDV infection can trigger a prominent increase of LGP2 mRNA expression in porcine cells; over-expression of LGP2 significantly suppressed FMDV replication; besides, LGP2 protein can be down-regulated by FMDV 2B and 3C protein in vivo. These results implied the antiviral activity of LGP2 against FMDV, and the downregulation of LGP2 induced by FMDV 2B and 3C protein possibly attenuated the antiviral activity of LGP2 during FMDV infection. To underline the involved antiviral mechanism induced by LGP2, in the future study, we will identify the functional domain and sites of LGP2 that involved in the antiviral effects. The signaling transduction mechanisms and the pathways activated by LGP2 during FMDV infection will be thoroughly determined and studied. We will also detect the interaction between LGP2 and FMDV viral proteins, and the interaction sites or regions will be determined. The antagonistic effects induced by viral proteins against LGP2-mediated antiviral responses will be further explored. Our study will stimulate insight into the antiviral roles of LGP2 in regulation of antiviral immune responses against FMDV.