Toll-Like Receptor 3 Mediates Establishment of an Antiviral State against Hepatitis C Virus in Hepatoma Cells
Toll-Like Receptor 3 Mediates Establishment of an Antiviral State against Hepatitis C Virus in Hepatoma Cells
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DOI：
10.1128/jvi.01125-09
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发表时间：
2009-10-01
影响因子：
5.4
通讯作者：
Li, Kui
中科院分区：
文献类型：
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作者：
Wang, Nan;Liang, Yuqiong;Li, Kui
toll样受体-3 （TLR3）感知双链RNA，启动激活nf - κ B和干扰素调节因子3 （IRF-3）的信号传导，从而诱导促炎细胞因子、I型干扰素和众多干扰素刺激基因（isg）的合成。这一途径尚未在人肝细胞中得到广泛研究，其在感知和保护肝炎病毒感染中的作用尚不确定。我们在这里表明，原代人肝细胞表达TLR3，并在poly(I)上强烈上调isg。C)刺激。我们还发现，当TLR3在允许型肝癌细胞中表达时，它能感知丙型肝炎病毒（HCV）感染，独立于视黄酸诱导基因I起作用，诱导IRF-3激活和isg合成，限制病毒复制。反过来，HCV感染降低了TRIF（一种重要的TLR3适配器）的丰度，并损害了poly(I)。全身的C)信号。HCV对TLR3信号的诱导和破坏可能是决定感染结果和HCV建立持续感染能力的重要因素。
Toll-like receptor-3 (TLR3) senses double-stranded RNA, initiating signaling that activates NF-kappa B and interferon regulatory factor 3 (IRF-3), thereby inducing the synthesis of proinflammatory cytokines, type I interferons, and numerous interferon-stimulated genes (ISGs). This pathway has not been extensively investigated in human hepatocytes, and its role in sensing and protecting against hepatitis virus infections is uncertain. We show here that primary human hepatocytes express TLR3 and robustly upregulate ISGs upon poly(I . C) stimulation. We also show that TLR3 senses hepatitis C virus (HCV) infection when expressed in permissive hepatoma cells, acting independently of retinoic acid-inducible gene I and inducing IRF-3 activation and the synthesis of ISGs that restrict virus replication. In turn, HCV infection reduces the abundance of TRIF, an essential TLR3 adaptor, and impairs poly(I . C)-induced signaling. The induction and disruption of TLR3 signaling by HCV may be important factors in determining the outcome of infection and the ability of HCV to establish persistent infections.