H9N2 Avian Influenza Virus Protein PB1 Enhances the Immune Responses of Bone Marrow-Derived Dendritic Cells by Down-Regulating miR375.
H9N2 Avian Influenza Virus Protein PB1 Enhances the Immune Responses of Bone Marrow-Derived Dendritic Cells by Down-Regulating miR375.
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DOI：
10.3389/fmicb.2017.00287
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发表时间：
2017
影响因子：
5.2
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
Lin J;Xia J;Tu CZ;Zhang KY;Zeng Y;Yang Q
聚合酶碱性蛋白1（PB 1）是甲型流感病毒RNA聚合酶复合物的催化核心，对病毒的转录和复制至关重要。树突状细胞（Dendritic cells，DCs）具有重要的抗原提呈能力，在识别和清除病毒中起重要作用。微小RNA（microRNA，miRNA）影响树突状细胞的发育、抗原提呈能力以及禽流感病毒（avian influenza virus，AIV）感染宿主细胞和复制的能力。在此，我们研究了miRNA介导的小鼠DCs免疫功能调节的分子机制。我们首先筛选并验证了PB 1转染后DC中miRNA的诱导。结果显示，病毒蛋白PB 1下调了DC中miR 375、miR 146、miR 339和miR 679的表达，与H9 N2病毒处理的结果一致;然而，病毒蛋白PB 1也下调了DC中miR 222和miR 499的表达，与H9 N2病毒处理的结果相反。我们的研究结果表明，PB 1增强了DC呈递抗原，激活淋巴细胞和分泌细胞因子的能力，而miR 375过表达抑制了DC成熟的激活。然而，一旦miR 375被抑制，PB 1就不能促进DC成熟。PB 1抑制P-Jnk/Jnk信号通路，激活p-Erk/Erk信号通路。抑制miR 375可激活p-Erk/Erk和p-p38/p38信号通路，但抑制P-Jnk/Jnk信号通路。总之，我们的研究结果揭示了PB 1和miR 375在调节DC功能中的作用和机制，并提出了对抗AIV的新策略。
Polymerase basic protein 1 (PB1), the catalytic core of the influenza A virus RNA polymerase complex, is essential for viral transcription and replication. Dendritic cells (DCs) possess important antigen presenting ability and a crucial role in recognizing and clearing virus. MicroRNA (miRNA) influence the development of DCs and their ability to present antigens as well as the ability of avian influenza virus (AIV) to infect host cells and replicate. Here, we studied the molecular mechanism underlying the miRNA-mediated regulation of immune function in mouse DCs. We first screened for and verified the induction of miRNAs in DCs after PB1 transfection. Results showed that the viral protein PB1 down-regulated the expression of miR375, miR146, miR339, and miR679 in DCs, consistent with the results of H9N2 virus treatment; however, the expression of miR222 and miR499, also reduced in the presence of PB1, was in contrast to the results of H9N2 virus treatment. Our results suggest that PB1 enhanced the ability of DCs to present antigens, activate lymphocytes, and secrete cytokines, while miR375 over-expression repressed activation of DC maturation. Nevertheless, PB1 could not promote DC maturation once miR375 was inhibited. Finally, we revealed that PB1 inhibited the P-Jnk/Jnk signaling pathway, but activated the p-Erk/Erk signaling pathway. While inhibition of miR375 -activated the p-Erk/Erk and p-p38/p38 signaling pathway, but repressed the P-Jnk/Jnk signaling pathway. Taken together, results of our studies shed new light on the roles and mechanisms of PB1 and miR375 in regulating DC function and suggest new strategies for combating AIV.