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Cell Res：舒红兵课题组发文，揭示抗病毒天然免疫新机制

2019-01-22 莉萝 病毒学界

抗病毒胆汁酸代谢
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为了找到细胞代谢与抗病毒天然免疫之间的相互调控机制，该课题组通过RNA-seq的方法检测单纯疱疹病毒HSV-1感染THP-1（人急性单核细胞白血病细胞）细胞后代谢相关基因的变化，并鉴定出胆汁酸代谢相关转运蛋白SLCO1A2和关键限速合成酶CYP7A1、CYP7B1和CYP27A1等基因的表达在病毒感染后被快速诱导。

1月16日，武汉大学医学研究院的舒红兵院士课题组在Cell Research杂志上在线发表题为Virus-induced accumulation of intracellular bile acids activates the TGR5-β-arrestin-SRC axis to enable innate antiviral immunity的论文，首次发现病毒感染诱导机体多种细胞中胆汁酸代谢基因的表达和胆汁酸的积累，并通过TGR5-β-arrestin-SRC信号通路促进抗病毒天然免疫反应的发生。

为了找到细胞代谢与抗病毒天然免疫之间的相互调控机制，该课题组通过RNA-seq的方法检测单纯疱疹病毒HSV-1感染THP-1（人急性单核细胞白血病细胞）细胞后代谢相关基因的变化，并鉴定出胆汁酸代谢相关转运蛋白SLCO1A2和关键限速合成酶CYP7A1、CYP7B1和CYP27A1等基因的表达在病毒感染后被快速诱导。

以前的研究表明，生理状态下机体中的胆汁酸生物合成一般只在肝脏细胞中进行。在这项研究中，舒红兵研究组发现，在包括免疫细胞在内的多种细胞中，病毒感染极早期就能够快速激活关键转录因子NF-κB，进而上调细胞中胆汁酸(BA)转运体和生物合成限速酶的基因表达，并且导致细胞中胆汁酸的积累（下图）。细胞中积累的胆汁酸进一步能够通过TGR5-GRK-β-arrestin通路激活蛋白络氨酸激酶SRC，从而调节抗病毒信号通路中多个关键蛋白的酪氨酸磷酸化修饰，包括VISA/MAVS和MITA/STING等，最终启动有效的抗病毒免疫反应。

动物实验表明，TGR5（Takeda G Protein Coupled Receptor-5）基因敲除的小鼠中单纯疱疹病毒HSV-1和脑心肌炎病毒EMCV感染诱导的I型干扰素等多种抗病毒细胞因子的表达水平显着降低，小鼠脑组织中的病毒滴度显着升高，病毒感染诱导TGR5基因敲除小鼠的死亡率明显升高，这说明TGR5基因敲除的小鼠抗病毒能力明显减弱。进一步研究表明，腹腔注射胆汁酸能够明显促进野生型小鼠的抗病毒能力，而对TGR5基因敲除的小鼠影响不大。这些发现揭示了病毒感染过程中机体细胞中胆汁酸代谢和抗病毒天然免疫信号通路之间相互调控的内在规律，并为开发胆汁酸及其类似物作为抗病毒药物提供了重要基础。

原始出处：Ming-Ming Hu, Wen-Rui He, Peng Gao, et al. Virus-induced accumulation of intracellular bile acids activates the TGR5-β-arrestin-SRC axis to enable innate antiviral immunity. Cell Res.  16 January 2019

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    2019-05-19 zhaozhouchifen

    #Cell#

    0

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    2019-04-23 维他命

    #CEL#

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    2019-01-23 yahu

    #抗病毒#

    0

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    2019-01-23 仁心济世

    #天然免疫#

    0

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