Porcine epidemic diarrhea virus infection induces NF-κB activation through the TLR2, TLR3 and TLR9 pathways in porcine intestinal epithelial cells
Porcine epidemic diarrhea virus infection induces NF-κB activation through the TLR2, TLR3 and TLR9 pathways in porcine intestinal epithelial cells
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DOI：
10.1099/vir.0.000133
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发表时间：
2015-07-01
影响因子：
3.8
通讯作者：
Li, Guangxing
中科院分区：
文献类型：
--
作者：
Cao, Liyan;Ge, Xuying;Li, Guangxing
猪流行性腹泻病毒（Porcine epidemic diarrhea virus，PEDV）是一种引起猪持续性腹泻的冠状病毒，在养猪国家造成严重的经济损失。深入了解PEDV感染和先天免疫系统之间的相互作用对于理解相关的发病机制是必要的。转录因子NF-κ B在调节宿主免疫应答中起重要作用。在这里，我们首次阐明了PEDV介导的NF-κ B激活猪小肠上皮细胞（IEC）的潜在机制。在PEDV感染期间，发现NF-κ B p65从细胞质易位到细胞核，并且PEDV依赖的NF-κ B活性与病毒剂量和活跃复制相关。使用小干扰RNA筛选Toll样受体（TLR）或RIG-I样受体信号传导途径的不同mRNA组分，我们证明TLR 2、TLR 3和TLR 9响应于PEDV感染而促进NF-κ B活化，但不促进RIG-I。通过筛选PEDV结构蛋白诱导NF-κ B活性的能力，我们发现PEDV核衣壳蛋白（N）可以激活NF-κ B，并且N的中心区域是NF-κ B激活所必需的。此外，TLR 2参与PEDV N诱导的IEC中NF-κ B活化。总的来说，这些发现为研究PEDV感染诱导的NF-κ B活化的分子机制提供了新的途径。
Porcine epidemic diarrhea virus (PEDV) is a coronavirus that induces persistent diarrhoea in swine, resulting in severe economic losses in swine-producing countries. Insights into the interplay between PEDV infection and the innate immune system are necessary for understanding the associated mechanism of pathogenesis. The transcription factor NF-kappa B plays an important role in regulating host immune responses. Here, we elucidated for the first time to our knowledge the potential mechanism of PEDV-mediated NF-kappa B activation in porcine small intestinal epithelial cells (IECs). During PEDV infection, NF-kappa B p65 was found to translocate from the cytoplasm to the nucleus, and PEDV-dependent NF-kappa B activity was associated with viral dose and active replication. Using small interfering RNAs to screen different mRNA components of the Toll-like receptor (TLR) or RIG-I-like receptor signalling pathways, we demonstrated that TLR2, TLR3 and TLR9 contribute to NF-kappa B activation in response to PEDV infection, but not RIG-I. By screening PEDV structural proteins for their ability to induce NF-kappa B activities, we found that PEDV nucleocapsid protein (N) could activate NF-kappa B and that the central region of N was essential for NF-kappa B activation. Furthermore, TLR2 was involved in PEDV N-induced NF-kappa B activation in IECs. Collectively, these findings provide new avenues of investigation into the molecular mechanisms of NF-kappa B activation induced by PEDV infection.