GP73 facilitates hepatitis B virus replication by repressing the NF-κB signaling pathway
GP73 facilitates hepatitis B virus replication by repressing the NF-κB signaling pathway
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GP73 通过抑制 NF-κB 信号通路促进乙型肝炎病毒复制
DOI：
10.1002/jmv.25718
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发表时间：
2020-02-28
影响因子：
12.7
通讯作者：
Liu, Zhixin
中科院分区：
文献类型：
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作者：
Liu, Long;Zhu, Jianyong;Liu, Zhixin
乙型肝炎病毒（HBV）慢性感染全世界约3.5亿人，60万人死于HBV相关的肝功能衰竭。高尔基蛋白73 （GP73）是肝脏疾病（包括慢性乙型肝炎）的血清生物标志物。在这里，我们确定了HBV感染对GP73产生的影响，并表征了GP73在HBV复制中的作用。最初，我们发现GP73在慢性肝病hbv阳性患者的血清和hbv刺激的白细胞中大量产生。此外，HBV刺激促进从健康供体分离的外周血单核细胞和从人急性单核白血病细胞（THP-1）衍生的巨噬细胞中GP73的产生。值得注意的是，激活GP73表达需要乙型肝炎表面抗原（HBsAg），而不是HBV复制。此外，在HepG2细胞和Huh7细胞中，GP73促进HBV复制并抑制核因子κ B p50的表达，进而抑制HBV复制和GP73的表达。最后，我们证明GP73通过抑制先天免疫反应和核因子κ B信号通路促进HBV复制。综上所述，我们揭示了HBV复制和GP73产生之间明显的正反馈机制，并表明GP73是HBV感染的潜在抗病毒靶点。
Hepatitis B virus (HBV) chronically infects approximately 350 million people worldwide, and 600 000 deaths are caused by HBV-related hepatic failure. Golgi protein 73 (GP73) is a serum biomarker for liver diseases, including chronic hepatitis B. Here, we determine the effect of HBV infection on GP73 production and characterized the role of GP73 in HBV replication. Initially, we show that GP73 is highly produced in the sera of HBV-positive patients with chronic liver diseases and in HBV-stimulated leukocytes. In addition, HBV stimulation promotes GP73 production in peripheral blood mononuclear cells isolated from healthy donors and in macrophages derived from human acute monocytic leukemia cells (THP-1). Notably, the hepatitis B surface antigen (HBsAg), but not HBV replication, is required for the activation of GP73 expression. Moreover, in HepG2 cells and Huh7 cells, GP73 facilitates HBV replication and represses nuclear factor kappa B p50 expression, which in turn represses HBV replication and GP73 expression. Finally, we demonstrate that GP73 facilitates HBV replication by repressing the innate immune response and the nuclear factor kappa B signaling pathway. Taken together, we revealed a distinct positive feedback mechanism between HBV replication and GP73 production and suggest that GP73 acts as a potential antiviral target for HBV infection.