HCV core protein binds to gC1qR to induce A20 expression and inhibit cytokine production through MAPKs and NF-κB signaling pathways.
HCV core protein binds to gC1qR to induce A20 expression and inhibit cytokine production through MAPKs and NF-κB signaling pathways.
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HCV 核心蛋白与 gC1qR 结合诱导 A20 表达并通过 MAPK 和 NF-kappa B 信号通路抑制细胞因子产生
DOI：
10.18632/oncotarget.9304
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发表时间：
2016-06-07
期刊：
影响因子：
--
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Song X;Yao Z;Yang J;Zhang Z;Deng Y;Li M;Ma C;Yang L;Gao X;Li W;Liu J;Wei L
丙型肝炎病毒感染的特点是有很强的慢性化倾向。在慢性丙型肝炎病毒感染过程中，丙型肝炎病毒核心蛋白参与了与慢性炎症相关的细胞因子表达的失控。A20是一种强大的细胞因子信号转导抑制因子，本研究探讨了丙型肝炎病毒核心蛋白诱导巨噬细胞表达A20及其信号转导途径。结果表明，丙型肝炎病毒核心蛋白可诱导巨噬细胞表达A20。沉默A20可显著增加IL-6、IL-1β和转化生长因子-β1的分泌，但对IL-8和肿瘤坏死因子的分泌无明显影响。此外，在下拉实验中，丙型肝炎病毒核心蛋白与gC1qR相互作用，而不与TLR2、TLR3和TLR4相互作用。沉默gC1qR可抑制核心诱导的A20表达。此外，丙型肝炎病毒核心蛋白激活了巨噬细胞中的MAPK、NF-κB和PI3K/AKT信号通路。抑制P38、JNK和NF-κB，但不抑制ERK和AKT活性，可显著降低A20的表达。综上所述，本研究提示丙型肝炎病毒核心蛋白通过P38、JNK和NF-κB信号通路与gC1qR结合，诱导巨噬细胞表达A20，从而导致丙型肝炎病毒感染时的轻度慢性炎症。它代表了一种新的机制，通过这种机制，丙型肝炎病毒篡夺了宿主的持久性。
Hepatitis C virus (HCV) infection is characterized by a strong propensity toward chronicity. During chronic HCV infection, HCV core protein is implicated in deregulating cytokine expression that associates with chronic inflammation. A20 is known as a powerful suppressor in cytokine signaling, in this study, we explored the A20 expression in macrophages induced by HCV core protein and the involved signaling pathways. Results demonstrated that HCV core protein induced A20 expression in macrophages. Silencing A20 significantly enhanced the secretion of IL-6, IL-1β and TGF-β1, but not IL-8 and TNF. Additionally, HCV core protein interacted with gC1qR, but not TLR2, TLR3 and TLR4 in pull-down assay. Silencing gC1qR abrogated core-induced A20 expression. Furthermore, HCV core protein activated MAPK, NF-κB and PI3K/AKT pathways in macrophages. Inhibition of P38, JNK and NF-κB but not ERK and AKT activities greatly reduced the A20 expression. In conclusion, the study suggests that HCV core protein ligates gC1qR to induce A20 expression in macrophages via P38, JNK and NF-κB signaling pathways, which leads to a low-grade chronic inflammation during HCV infection. It represents a novel mechanism by which HCV usurps the host for persistence.
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影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia
影响因子：
20.3
作者：
Hagemann T;Biswas SK;Lawrence T;Sica A;Lewis CE
通讯作者：
Lewis CE
影响因子：
3.7
作者：
O'Beirne, James;Mitchell, Jon;Harrison, Phillip M.
通讯作者：
Harrison, Phillip M.
对HCV和其他肝炎病毒的免疫反应。
影响因子：
32.4
作者：
Park, Su-Hyung;Rehermann, Barbara
通讯作者：
Rehermann, Barbara
影响因子：
4.9
作者：
Park, Kyung R.;Bryers, James D.
通讯作者：
Bryers, James D.