甲型流感病毒感染野生型和Ifitm3^-/^-小鼠的纵膈淋巴结的转录组学研究  

Transcriptome Profiling of Influenza A Virus Infected Draining Lymph Nodes of Ifitm3^-/^- and Wild Type Mice

作　　者：孙强 雷娜[2] 鲁健 路环环[2] 刘淑慧 舒跃龙 SUN Qiang;LEI Na;LU Jian;LU Huanhuan;LIU Shuhui;SHU Yuelong(School of Public Health(Shenzhen),Sun Yat⁃sen University,Guangdong 510275,China;National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Prevention and Control,Key Laboratory for Medical Virology,National Health Commission,Beijing 102206,China)

机构地区：[1]中山大学公共卫生学院(深圳),广州510275 [2]中国疾病预防控制中心病毒病预防控制所,国家卫生健康委员会医学病毒和病毒病重点实验室,北京102206

出　　处：《病毒学报》2020年第3期415-420,共6页Chinese Journal of Virology

基　　金：国家杰出青年科学基金项目(项目号:81525017),题目:流感病原生物学研究;国家自然青年科学基金(项目号:31900140),题目:宿主IFITM3蛋白精氨酸甲基化修饰调节抗流感病毒作用研究。

摘　　要：干扰素诱导的跨膜蛋白3(Interferon-induced transmembrane protein 3,IFITM3)敲除小鼠(Ifitm3^-/^-小鼠)感染流感病毒后,表现出更为严重的病理损伤和死亡率。最近的研究发现,IFITM3蛋白表达也会影响机体针对流感病毒的适应性免疫反应效果。由于空间效应,纵膈淋巴结在机体抵抗流感病毒急性期感染的适应性免疫应答过程中发挥重要功能,本研究欲探究使用流感病毒鼠肺适应株A/PR/8/H1N1进行感染后,野生型和Ifitm3^-/^-小鼠的纵膈淋巴结中与免疫相关的差异表达基因。本研究对流感病毒PR8感染后第3d的纵膈淋巴结进行RNA-Seq测序。高通量测序共检测到有1312个差异表达基因,其中上调和下调差异表达基因分别为904和408个。这些差异表达基因主要参与炎症反应与细胞凋亡信号通路、T细胞和B细胞受体信号通路、T细胞和B细胞激活与细胞因子分泌等信号通路。采用荧光定量PCR对部分免疫相关的差异表达基因进行验证,结果与RNA-Seq测序结果一致。本研究为进一步阐明IFITM3在适应性免疫应答中拮抗流感病毒的分子机制奠定了基础。Ifitm3-/-mice showed more severe pathologic damage and mortality after infection by influenza viruses than that before infection. Recent studies have suggested that interferon-induced transmembrane protein 3(IFITM3) expression also affects the body’s adaptive immune response to influenza viruses. Due to the"space effect",mediastinal lymph nodes play an important part in the body’s adaptive immune response against acute respiratory infections caused by influenza viruses. We wished to measure expression of immune-related differentially expressed genes(DEGs)in the mediastinal lymph nodes of wild type and Ifitm3-/-mice. RNA sequencing(RNA-Seq)was carried out 3 days after infection with lung-adapted influenza virus A/PR/8/H1N1.A total of 1,312 DEGs were detected by high-throughput sequencing,of which 904 were up-regulated and 408 were down-regulated,respectively. These DEGs were involved mainly in signaling pathways:inflammatory response and apoptosis;T-and B-cell receptors;T-and B-cell activation and cytokine secretion. Immunerelated DEGs were identified by real-time PCR,and the results were consistent with RNA-Seq results. Our study provided clues on the anti-influenza-related to adaptive immune response of IFITM3 in the draining lymph nodes.

关 键 词：流感病毒 干扰素诱导的跨膜蛋白3(IFITM3) 纵膈淋巴结 RNA-SEQ 差异表达基因 

分 类 号：R313.1[医药卫生—基础医学]