新冠病毒NSP9蛋白通过靶向宿主mRNA出核转运调控TLR7天然免疫响应
SARS-CoV-2 NSP9 Protein Regulates TLR7 Innate Immune Response by Targeting Host mRNA Nuclear Export Pathway
新型冠状病毒（Severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）的非结构蛋白在病毒感染进程中发挥重要作用，但其调控宿主天然免疫响应的分子机制仍需进一步的研究。模式识别受体Toll样受体在抗病毒天然免疫响应中发挥重要作用，本研究探究SARS-CoV-2感染进程中NSP蛋白通过干预宿主TLR通路实现对宿主天然免疫效应的影响及相关机制。双荧光素酶报告基因实验结果显示NSP9蛋白可显著抑制TLR7下游的免疫响应。进一步研究表明，NSP9可显著抑制宿主部分mRNA从细胞核向细胞质的运输。核质分离实验结合转录组分析结果显示，NSP9显著降低了TLR7下游效应因子mRNA在细胞质的比例。综上，本研究发现SARS-CoV-2 NSP9可以通过靶向mRNA出核转运通路实现对TLR7通路下游免疫效应因子表达的抑制，研究结果为SARS-CoV-2的防治提供了理论基础和潜在靶点。
he SARS-CoV-2 non-structural proteins (NSPs) play crucial roles during virus infection, But its molecular mechanisms regulating host innate immune response still require further research, including the Toll-like receptor signaling and downstream immune responses, remain unclear. This study aims to explore the influence of NSP proteins on the innate immune response of the host downstream of TLR signaling. The results from the dual-luciferase reporter assay indicate that overexpression of NSP9 significantly inhibits the NF-κB signaling downstream of TLR7. Further research shows that NSP9 expression significantly inhibits the host mRNA nuclear export. In summary, our study reveals NSP9 as a virulence factor to inhibit TLR7-dependent response of the host by targeting cellular mRNA nuclear export, providing a theoretical basis and potential targets for the prevention and treatment of SARS-CoV-2.
毛锐、张珂、刘博、庞刚
基础医学分子生物学微生物学
新型冠状病毒天然免疫oll样受体非结构蛋白
SARS-CoV-2Innate immunityToll-like receptorNon-structural protein
毛锐,张珂,刘博,庞刚.新冠病毒NSP9蛋白通过靶向宿主mRNA出核转运调控TLR7天然免疫响应[EB/OL].(2024-04-19)[2025-08-04].http://www.paper.edu.cn/releasepaper/content/202404-221.点此复制
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