Lin Jian, Xia Jing, Tu Chong Z, Zhang Ke Y, Zeng Yan, Yang Qian
Department of Zoology, College of Life Science, Nanjing Agricultural University Jiangsu, China.
Department of Histoembryology, College of Veterinary Medicine, Nanjing Agricultural University Jiangsu, China.
Front Microbiol. 2017 Mar 22;8:287. doi: 10.3389/fmicb.2017.00287. eCollection 2017.
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.
聚合酶碱性蛋白1（PB1）是甲型流感病毒RNA聚合酶复合物的催化核心，对病毒转录和复制至关重要。树突状细胞（DCs）具有重要的抗原呈递能力，在识别和清除病毒中起关键作用。微小RNA（miRNA）影响DCs的发育及其呈递抗原的能力，以及禽流感病毒（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PB1转染后DCs中miRNA的诱导情况。结果表明，病毒蛋白PB1下调了DCs中miR375、miR146、miR339和miR679的表达，这与H9N2病毒处理的结果一致；然而，在PB1存在下也降低的miR222和miR499的表达与H9N2病毒处理的结果相反。我们的结果表明，PB1增强了DCs呈递抗原、激活淋巴细胞和分泌细胞因子的能力，而miR375的过表达抑制了DC成熟的激活。然而，一旦miR375被抑制，PB1就不能促进DC成熟。最后，我们发现PB1抑制P-Jnk/Jnk信号通路，但激活p-Erk/Erk信号通路。而抑制miR375则激活p-Erk/Erk和p-p38/p38信号通路，但抑制P-Jnk/Jnk信号通路。综上所述，我们的研究结果为PB1和miR375在调节DC功能中的作用和机制提供了新的见解，并为对抗AIV提出了新的策略。
