School of Basic Medical Sciences, Department of Respiratory, Department of Infectious Diseases, Renmin Hospital, Hubei University of Medicine, Shiyan, China.
Department of Emergency, Dongfeng Maojian Hospital, Sinopharm Group Corporation, Shiyan, China.
J Med Virol. 2020 Dec;92(12):3327-3335. doi: 10.1002/jmv.25718. Epub 2020 Feb 28.
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.
乙型肝炎病毒（HBV）在全球范围内慢性感染约 3.5 亿人，其中 60 万人死于 HBV 相关肝衰竭。高尔基糖蛋白 73（GP73）是一种血清生物标志物，可用于诊断包括慢性乙型肝炎在内的多种肝脏疾病。本研究旨在探究 HBV 感染对 GP73 产生的影响，并对 GP73 在 HBV 复制过程中的作用进行了研究。首先，我们发现慢性肝脏疾病 HBV 阳性患者的血清中以及 HBV 刺激的白细胞中高度表达 GP73。此外，HBV 刺激可促进健康供者外周血单个核细胞和源自人急性单核细胞白血病细胞（THP-1）的巨噬细胞中 GP73 的产生。值得注意的是，HBsAg（而非 HBV 复制）是激活 GP73 表达所必需的。此外，在 HepG2 细胞和 Huh7 细胞中，GP73 可促进 HBV 复制并抑制核因子 kappa B p50 的表达，进而抑制 HBV 复制和 GP73 表达。最后，我们证明 GP73 通过抑制固有免疫反应和核因子 kappa B 信号通路促进 HBV 复制。综上，本研究揭示了 HBV 复制与 GP73 产生之间的独特正反馈机制，并提示 GP73 可能成为 HBV 感染的潜在抗病毒治疗靶点。
