乙型肝炎病毒抑制肝细胞免疫检查点PD-1配体基因表达的研究

发布时间：2018-05-02 18:44

本文选题：肝炎病毒 + 乙型　；参考：《重庆医学》2017年27期

【摘要】：目的在细胞水平上分析乙型肝炎病毒(HBV)复制及其编码的X基因(HBx)表达对细胞基因表达谱的影响,特别是免疫相关基因表达水平的变化。方法通过慢病毒和pcDNA瞬时转染过表达HBx基因,利用RNA-Seq和RT-qPCR等方法检测免疫相关基因的表达水平,并在HBV复制细胞系中进行验证。结果 HBV复制和HBx表达可以剂量依赖性抑制免疫检查点程序性死亡分子1(PD-1)配体基因(PD-L1/CD274)的表达,而HBx基因的H-box突变体的表达失去该抑制效应。结论HBV/HBx具有抑制PD-L1/CD274基因表达的能力,在病毒感染的急性期解除抗原特异性T细胞激活的检查点,活化细胞毒性T细胞,这可能导致T细胞对高度复制的细胞进行攻击和清除,帮助病毒进入较低复制状态,达到病毒-宿主的平衡状态并奠定HBV慢性感染的基础。
[Abstract]:Objective to investigate the effect of HBV replication and its X gene expression on cell gene expression profile at cellular level, especially the changes of immune-related gene expression level. Methods the expression level of immune-related genes was detected by RNA-Seq and RT-qPCR, and verified in HBV replication cell line by transient transfection of HBx gene by lentivirus and pcDNA. Results HBV replication and HBx expression could inhibit the expression of PD-L1 / CD274) in a dose-dependent manner, while the expression of H-box mutants of HBx gene lost the inhibitory effect. Conclusion HBV/HBx has the ability to inhibit the expression of PD-L1/CD274 gene, deactivate the checkpoint of antigen-specific T cell activation and activate cytotoxic T cells in the acute phase of viral infection, which may lead to T cells attacking and clearing highly duplicated cells. To help the virus into a low replication state, to achieve a virus-host balance and to lay the foundation for chronic HBV infection.
【作者单位】：西南民族大学药学院;四川大学华西第二医院;四川省德阳市人民医院肝胆外科;
【基金】：四川省科技厅科技支撑项目(2017FZ0034) 四川省卫生和计划生育委员会基金资助项目(16PJ144) 国家级大学生创新创业训练计划项目(201610656073)
【分类号】：R512.62

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