HCoV-OC43逃避人树突状细胞免疫清除机制的初步研究

发布时间：2018-08-23 14:36

【摘要】：目的:了解人冠状病毒OC43(Human coronavirus OC43,HCoV-OC43)逃避人树突状细胞(Dendritic cell,DC)免疫监视作用的初步机制。方法:利用HCoV-OC43阳性病人的标本感染BSC-1细胞分离OC43病毒,相差显微镜观察细胞病变(Cytopathic effect,CPE),实时荧光定量聚合酶链反应(Real-time PCR)进行鉴定;利用人细胞因子GM-CSF和IL-4联合体外诱导DC分化,于诱导7 d后用HCoV-OC43病毒感染DC。采用透射电镜观察DC感染后的形态,Real-time PCR检测DC功能相关细胞因子的表达水平;流式细胞术检测DC比例及其功能相关共刺激分子的表达。结果:成功建立HCoV-OC43体外感染DC的体系。HCoV-OC43能感染DC并刺激其产生免疫应答,但培养上清中不能检测到病毒核酸;HCoV-OC43感染会导致DC细胞表达IFN-α、IFN-β、CCL3和CCL5的量显著下调,但其共刺激分子HLA-DR、CD1c和CD86的表达不受抑制。结论:HCoVOC43可感染人DC细胞并刺激其产生免疫应答,但不能产生活的子代病毒;HCoV-OC43可通过抑制宿主DC细胞IFN-α等相关炎症因子和趋化因子的分泌,来实现免疫逃逸。
[Abstract]:Aim: to investigate the mechanism of human coronavirus OC43 (Human coronavirus OC43 (HCoV-OC43) escaping the immune surveillance of human Dendritic cells. Methods: OC43 virus was isolated from BSC-1 cells infected with HCoV-OC43 positive patients, detected by phase contrast microscope and identified by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), differentiation of DC was induced by human cytokine GM-CSF and IL-4 combination. After 7 days of induction, DC2 was infected with HCoV-OC43 virus. The expression of DC function-related cytokines and the ratio of DC and the expression of function-related costimulatory molecules were detected by transmission electron microscopy (TEM) and real-time PCR. Results: the system of DC infected with HCoV-OC43 in vitro. HCoV-OC43 could infect DC and stimulate its immune response. However, the infection of HCoV-OC43 could significantly down-regulate the expression of IFN- 伪 -IFN- 尾 CCL3 and CCL5 in DC cells. However, the expression of HLA-DRN CD1c and CD86 was not inhibited. ConclusionHCoVOC43 can infect human DC cells and stimulate them to produce immune response, but HCoV-OC43 can prevent immune escape by inhibiting the secretion of IFN- 伪 and other related inflammatory factors and chemokines in host DC cells.
【作者单位】：广州医科大学基础学院病原生物学与免疫学教研室;中山大学热带病防治研究教育部重点实验室;中山大学香港大学粤港传染病监测联合实验室;中山大学附属第一医院MICU室;
【基金】：国家传染病防治科技重大专项(No.2012ZX10004-213) 国家自然科学基金项目(No.81000230) 广东省自然科学基金青年项目(No.A030310282)资助
【分类号】：R392

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