The antigen-presenting ability of dendritic cells (DCs) plays an important and irreplaceable role in recognising and clearing viruses. Antiviral responses must rapidly defend against infection while minimising inflammatory damage, but the mechanisms that regulate the magnitude of response within an infected cell are not well understood. MicroRNAs (microRNAs), small non-coding RNAs, can regulate mouse or avian DCs to inhibit the infection and replication of avian influenza virus (AIV). Here, we performed a global analysis to understand how avian DCs respond to H9N2 AIV and provide a potential mechanism to explain how avian microRNAs can defend against H9N2 AIV replication. First, we found that both active and inactive H9N2 AIV enhanced the ability of DCs to present antigens and activate T lymphocytes. Next, total microarray analyses suggested that H9N2 AIV stimulation involved protein localisation, nucleotide binding, leucocyte transendothelial migration and MAPK signalling. Moreover, we constructed 551 transcription factor (TF)-miRNA-mRNA loops based on the above analyses. Furthermore, we found that the haemagglutinin (HA) fragment, neither H5N1-HA or H9N2-HA, could not activate DCs, while truncated HA greatly increased the immune function of DCs by activating ERK and STAT3 signalling pathways. Lastly, our results not only suggested that gga-miR1644 targets muscleblind-like protein 2 (MBNL2) to enhance the ability of avian DCs to inhibit virus replication, but also suggested that gga-miR6675 targets the nuclear localisation sequence of polymerase basic protein 1 (PB1) to trigger the silencing of PB1 genes, resulting in the inhibition of H9N2 AIV replication. Altogether, our innovative study will shed new light on the role of avian microRNAs in evoking avian DCs and inhibiting virus replication.

中文翻译：

---

microRNA的全基因组分析揭示了对H9N2禽流感病毒与禽树突状细胞之间相互作用的新颖见解。

树突状细胞（DC）的抗原呈递能力在识别和清除病毒中起着重要且不可替代的作用。抗病毒反应必须在最小化炎症损害的同时迅速防御感染，但是调节感染细胞内反应强度的机制尚不十分清楚。MicroRNA（microRNA）是小的非编码RNA，可以调节小鼠或禽类DC，以抑制禽流感病毒（AIV）的感染和复制。在这里，我们进行了一项全局分析，以了解禽类DC如何响应H9N2 AIV，并提供了一种潜在的机制来解释禽类microRNA如何防御H9N2 AIV复制。首先，我们发现有活性和无活性的H9N2 AIV均可增强DC呈递抗原和激活T淋巴细胞的能力。下一个，总体芯片分析表明，H9N2 AIV刺激涉及蛋白质定位，核苷酸结合，白细胞跨内皮迁移和MAPK信号传导。此外，基于上述分析，我们构建了551个转录因子（TF）-miRNA-mRNA环。此外，我们发现血凝素（HA）片段，既不是H5N1-HA也不是H9N2-HA，都不能激活DC，而截短的HA通过激活ERK和STAT3信号通路大大增强了DC的免疫功能。最后，我们的结果不仅表明gga-miR1644靶向肌肉盲样蛋白2（MBNL2）以增强禽类DC抑制病毒复制的能力，还表明gga-miR6675靶向聚合酶基础蛋白1的核定位序列（ PB1）触发PB1基因沉默，导致抑制H9N2 AIV复制。总之，我们的创新研究将为禽类microRNA在唤起禽类DC和抑制病毒复制中的作用提供新的思路。