Lin Jian, Xia Jing, Chen Ya T, Zhang Ke Y, Zeng Yan, Yang Qian
College of Life Science, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China.
College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing, Jiangsu 210095, PR China.
Vaccine. 2017 Feb 1;35(5):729-737. doi: 10.1016/j.vaccine.2016.12.054. Epub 2017 Jan 4.
Avian influenza virus (AIV) of the subtypes H9 and N2 is well recognised and caused outbreaks-due to its high genetic variability and high rate of recombination with other influenza virus subtypes. The pathogenicity of H9N2 AIV depends on the host immune response. Dendritic cells (DCs) are major antigen presenting cells that can significantly inhibit H9N2 AIV replication. MicroRNAs (miRNAs) influence the ability of DCs to present antigens, as well as the ability of AIVs to infect host cells and replicate. Here, we studied the molecular mechanism underlying the miRNA-mediated regulation of immune function of mouse DCs. We first screened for and verified the induction of miRNAs in DCs after H9N2 AIVstimulation. We also constructed miR29c, miR339 and miR222 over-expression vector and showed that only the induction of miR29c lead to a hugely increased expression of surface marker MHCII and CD40. Whilst the inhibition of miR29c, miR339 and miR222 in mouse DCs would repressed the expression of DCs surface markers. Moreover, we found that miR29c stimulation not only up-regulate MHCII and CD40, but also enhance the ability of DCs to activate lymphocytes and secrete cytokines IL-6 or TNF-a. Furthermore, we found that Tarbp1 and Rfx7 were targeted and repressed by miR29c. Finally, we revealed that the inhibition of miR29c marvelously accelerated virus replication. Together, our data shed new light on the roles and mechanisms of miR29c in regulating DC function and suggest new strategies for combating AIVs.
H9和N2亚型禽流感病毒（AIV）因其高度的基因变异性以及与其他流感病毒亚型的高重组率而广为人知，并引发了疫情。H9N2 AIV的致病性取决于宿主的免疫反应。树突状细胞（DCs）是主要的抗原呈递细胞，能够显著抑制H9N2 AIV的复制。微小RNA（miRNAs）影响DCs呈递抗原的能力，以及AIV感染宿主细胞并进行复制的能力。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H9N2 AIV刺激后DCs中miRNAs的诱导情况。我们还构建了miR29c、miR339和miR222过表达载体，并表明只有miR29c的诱导导致表面标志物MHCII和CD40的表达大幅增加。而在小鼠DCs中抑制miR29c、miR339和miR222会抑制DCs表面标志物的表达。此外，我们发现miR29c刺激不仅上调MHCII和CD40，还增强了DCs激活淋巴细胞并分泌细胞因子IL-6或TNF-α的能力。此外，我们发现Tarbp1和Rfx7是miR29c的靶标并受到其抑制。最后，我们揭示抑制miR29c能显著加速病毒复制。总之，我们的数据为miR29c在调节DC功能中的作用和机制提供了新的见解，并为对抗AIVs提出了新策略。
