Reticuloendotheliosis virus (REV) infection of multiple avian species can lead to a number of diseases such as runting syndrome, immunosuppression and oncogenesis, causing major economic losses. MicroRNAs play important roles in post-transcriptional regulation, effectively inhibiting protein synthesis, and participating in many biological processes in cells, including proliferation, differentiation, apoptosis, lipometabolism, virus infection and replication, and tumorigenesis. Based on our previous high-throughput sequencing results, we explore the regulatory mechanisms of microRNA-155(miR-155) in chicken embryo fibroblasts (CEFs) in response to REV infection. Our results revealed expression of miR-155 in CEFs after REV infection upregulated in a time- and dose-dependent manner, indicating miR-155 plays a role in REV infection in CEFs indeed. After transfected with miR-155-mimic and miR-155-inhibitor, we found overexpression of miR-155 targeted caspase-6 and FOXO3a to inhibit apoptosis and accelerate cell cycle, thus improving viability of REV-infected CEFs. This result also verified the protective role of miR-155 in the viability of CEFs in the presence of REV. Knockdown of miR-155 also supported these above conclusions. Our findings uncover a new mechanism of REV pathogenesis in CEFs, and also provide a theoretical basis for uncovering new effective treatment and prevention methods for RE based on miR-155.

中文翻译：

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鸡胚成纤维细胞中microRNA-155对网状内皮细胞病毒感染的调控机制。

网状内皮内皮病病毒（REV）感染多种禽类会导致许多疾病，如矮小综合症，免疫抑制和肿瘤发生，造成重大的经济损失。MicroRNA在转录后调节，有效抑制蛋白质合成以及参与细胞的许多生物学过程（包括增殖，分化，凋亡，脂肪代谢，病毒感染和复制以及肿瘤发生）中起重要作用。基于我们之前的高通量测序结果，我们探讨了鸡胚成纤维细胞（CEFs）中microRNA-155（miR-155）对REV感染的调控机制。我们的结果显示，REV感染以时间和剂量依赖性方式上调后，CEF中miR-155的表达，这表明miR-155确实在CEF中的REV感染中起作用。在用miR-155模拟物和miR-155抑制剂转染后，我们发现miR-155靶向的caspase-6和FOXO3a的过表达抑制凋亡并加速细胞周期，从而提高了REV感染的CEF的活力。该结果还证实了在存在REV的情况下，miR-155在CEF生存能力中的保护作用。敲低miR-155也支持上述结论。我们的发现揭示了CEF中REV发病机理的新机制，并为揭示基于miR-155的RE的新有效治疗和预防方法提供了理论基础。该结果还证实了在存在REV的情况下，miR-155在CEF生存能力中的保护作用。敲低miR-155也支持上述结论。我们的发现揭示了CEF中REV发病机理的新机制，并为揭示基于miR-155的RE的新有效治疗和预防方法提供了理论基础。该结果还证实了在存在REV的情况下，miR-155在CEF生存能力中的保护作用。敲低miR-155也支持上述结论。我们的发现揭示了CEF中REV发病机理的新机制，并为揭示基于miR-155的RE的新有效治疗和预防方法提供了理论基础。