Department of Microbiology, Harbin Medical University, Harbin 150081, China.
Department of Cell Biology, Harbin Medical University, Harbin 150081, China.
RNA. 2020 Jan;26(1):91-100. doi: 10.1261/rna.071985.119. Epub 2019 Nov 1.
Coxsackievirus B (CVB) is the major cause of human myocarditis and dilated cardiomyopathy. Toll-like receptor 3 (TLR3) is an intracellular sensor to detect pathogen's dsRNA. TLR3, along with TRAF6, triggers an inflammatory response through NF-κB signaling pathway. In the cells infected with CVB type 3 (CVB3), the abundance of miR-146a was significantly increased. The role of miR-146a in CVB infection is unclear. In this study, TLR3 and TRAF6 were identified as the targets of miR-146a. The elevated miR-146a inhibited NF-κB translocation and subsequently down-regulated proinflammatory cytokine expression in the CVB3-infected cells. Therefore, the NF-κB pathway can be doubly blocked by miR-146a through targeting of TLR3 and TRAF6. MiR-146a may be a negative regulator on inflammatory response and an intrinsic protective factor in CVB infection.
柯萨奇病毒 B（CVB）是人类心肌炎和扩张型心肌病的主要病因。Toll 样受体 3（TLR3）是一种细胞内传感器，可检测病原体的 dsRNA。TLR3 与 TRAF6 通过 NF-κB 信号通路触发炎症反应。在感染 CVB 型 3（CVB3）的细胞中，miR-146a 的丰度显著增加。miR-146a 在 CVB 感染中的作用尚不清楚。在这项研究中，TLR3 和 TRAF6 被确定为 miR-146a 的靶标。升高的 miR-146a 抑制了 NF-κB 易位，并随后下调了 CVB3 感染细胞中促炎细胞因子的表达。因此，NF-κB 通路可以通过靶向 TLR3 和 TRAF6 被 miR-146a 双重阻断。miR-146a 可能是 CVB 感染中炎症反应的负调节剂和内在保护因子。
