Activation of Toll-like receptor 3 inhibits Marek's disease virus infection in chicken embryo fibroblast cells
Activation of Toll-like receptor 3 inhibits Marek's disease virus infection in chicken embryo fibroblast cells
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Toll样受体3的激活抑制鸡胚成纤维细胞中马立克氏病病毒感染
DOI：
10.1007/s00705-015-2674-x
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发表时间：
2016-03-01
影响因子：
2.7
通讯作者：
Ye, Jianqiang
中科院分区：
文献类型：
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作者：
Hu, Xuming;Zou, Haitao;Ye, Jianqiang
Toll 样受体 3 (TLR3) 是抵抗病毒感染的先天免疫系统的重要组成部分，并控制适应性免疫的激活。 TLR3 在马立克氏病病毒 (MDV) 感染中的作用尚不清楚。在这项研究中，我们发现感染MDV的鸡胚成纤维细胞（CEF）中TLR3 mRNA的丰度显着高于对照组。通过 TLR3 配体刺激激活的 TLR3 信号传导抑制了 CEF 细胞中 MDV RB1B 株的复制。相反，转染TLR3 siRNA的CEF细胞促进RB1B感染和复制。然而，其他 TLR 配体的治疗，无论是刺激性（LPS、咪喹莫特和 CpG）还是抑制性（TLR2/4 抑制剂和/或 MyD88 抑制剂），对 RB1B 感染和复制几乎没有影响。此外，我们发现RB1B感染的CEF细胞中TLR3 mRNA的表达趋势与mdv1-mir-M4-5p（MDV编码的致癌miR-155的功能直系同源物）相似。与此不一致的是，在 96 hpi 时，RB1B 感染的 CEF 细胞中 TLR3 蛋白水平急剧降低，而 miR-M4-5p 在同一时间点至少增加了 200 倍。此外，用 mdv1-mir-M4-5p 模拟物转染的 CEF 细胞促进 RB1B 感染和复制，而 mdv1-mir-M4-5p 抑制剂则抑制 RB1B 感染和复制。在用 gga-miR-155 模拟物或抑制剂转染的 CEF 细胞中观察到类似的结果。这些发现表明 TLR3 和 MDV 编码的 miRNA 可能参与 MDV 感染。
Toll-like receptor 3 (TLR3) is a critical component of the innate immune system against viral infection and controls the activation of adaptive immunity. The role of TLR3 in Marek's disease virus (MDV) infection is not clear. In this study, we found that the abundance of TLR3 mRNA was significantly higher in chicken embryo fibroblast cells (CEF) infected with MDV than in a control group. Activated TLR3 signaling via TLR3 ligand stimulation inhibited replication of the RB1B strain of MDV in CEF cells. In contrast, CEF cells transfected with TLR3 siRNA promoted RB1B infection and replication. However, treatment with other TLR ligands, whether stimulatory (LPS, imiquimod and CpG) or inhibitory (TLR2/4 inhibitor and/or MyD88 inhibitor), had little effect on RB1B infection and replication. In addition, we found that the expression trend of TLR3 mRNA in RB1B-infected CEF cells was similar to that of mdv1-mir-M4-5p (a functional ortholog of oncogenic miR-155 encoded by MDV). Inconsistent with this, the TLR3 protein level was sharply reduced in RB1B-infected CEF cells at 96 hpi, while there was an at least 200-fold increase in miR-M4-5p at the same time point. Additionally, CEF cells transfected with an mdv1-mir-M4-5p mimic promoted RB1B infection and replication, while an mdv1-mir-M4-5p inhibitor inhibited RB1B infection and replication. Similar results were observed in CEF cells transfected with a gga-miR-155 mimic or inhibitor. These findings suggest that TLR3 and MDV-encoded miRNAs might be involved in MDV infection.