PDF(Pubmed)
Abstract：
Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enterovirus 71 (EV71) that frequently affects children, leading to severe infections in some cases. In general, when infection occurs, the body upregulates inflammatory responses to eliminate pathogenic microorganisms to protect the host from infection. However, EV71 may inhibit host\'s innate immunity to promote virus infection. At present, it is not fully understood how EV71 hijack the host cells for its own replication. Toll-like receptor 4 (TLR4), a natural immune receptor, historically associated with bacterial endotoxin-induced inflammatory responses. However, it is still unclear whether and how TLR4 is altered during EV71 infection. In this study, we observed a reduction in both TLR4 protein and gene transcript levels in RD, GES-1, and Vero cells following EV71 infection, as detected by RT-qPCR, immunofluorescence staining and western blot. Furthermore, we observed that the TLR4 downstream molecules of MYD88, p-NF-κB p65, p-TBK1 and related inflammatory cytokines were also reduced, suggesting that antiviral innate immune and inflammatory response were suppressed. To determine the impact of TLR4 changes on EV71 infection, we interfered EV71-infected RD cells with TLR4 agonist or inhibitor and the results showed that activation of TLR4 inhibited EV71 replication, while inhibition of TLR4 promote EV71 replication. Besides, EV71 replication was also promoted in TLR4 siRNA-transfected and EV71-infected RD cells. This suggests that down-regulation the expression of TLR4 by EV71 can inhibit host immune defense to promote EV71 self-replication. This novel mechanism may be a strategy for EV71 to evade host immunity.
摘要：
手,脚,和口蹄疫（HFMD）是由肠道病毒71（EV71）引起的常见传染病，经常影响儿童，在某些情况下导致严重感染。总的来说,当感染发生时，身体上调炎症反应以消除病原微生物，保护宿主免受感染。然而,EV71可能抑制宿主的先天免疫以促进病毒感染。目前,尚不完全了解EV71如何劫持宿主细胞进行自身复制。Toll样受体4(TLR4),天然免疫受体，历史上与细菌内毒素诱导的炎症反应相关。然而,目前尚不清楚在EV71感染期间TLR4是否以及如何改变.在这项研究中,我们在RD中观察到TLR4蛋白和基因转录水平的降低，EV71感染后的GES-1和Vero细胞，通过RT-qPCR检测，免疫荧光染色和蛋白质印迹。此外，我们观察到MYD88的TLR4下游分子、p-NF-κBp65、p-TBK1和相关炎性细胞因子也减少,提示抗病毒先天性免疫和炎症反应被抑制。为了确定TLR4变化对EV71感染的影响，我们用TLR4激动剂或抑制剂干扰EV71感染的RD细胞，结果表明TLR4的激活抑制了EV71的复制，而抑制TLR4促进EV71复制。此外,在TLR4siRNA转染和EV71感染的RD细胞中也促进了EV71的复制。这表明EV71下调TLR4的表达可以抑制宿主的免疫防御以促进EV71的自我复制。这种新机制可能是EV71逃避宿主免疫的一种策略。
