The hepatitis C virus (HCV) is a major cause of liver diseases ranging from liver inflammation to advanced liver diseases like cirrhosis and hepatocellular carcinoma (HCC). HCV infection is restricted to the liver, and more specifically to hepatocytes, which represent around 80% of liver cells. The mechanism of HCV entry in human hepatocytes has been extensively investigated since the discovery of the virus 30 years ago. The entry mechanism is a multi-step process relying on several host factors including heparan sulfate proteoglycan (HSPG), low density lipoprotein receptor (LDLR), tetraspanin CD81, Scavenger Receptor class B type I (SR-BI), Epidermal Growth Factor Receptor (EGFR) and Niemann-Pick C1-like 1 (NPC1L1). Moreover, in order to establish a persistent infection, HCV entry is dependent on the presence of tight junction (TJ) proteins Claudin-1 (CLDN1) and Occludin (OCLN). In the liver, tight junction proteins play a role in architecture and homeostasis including sealing the apical pole of adjacent cells to form bile canaliculi and separating the basolateral domain drained by sinusoidal blood flow. In this review, we will highlight the role of liver tight junction proteins in HCV infection, and we will discuss the potential targeted therapeutic approaches to improve virus eradication.

中文翻译：

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丙型肝炎病毒感染和紧密连接蛋白：结合的纽带。

丙型肝炎病毒 (HCV) 是肝脏疾病的主要原因，从肝脏炎症到肝硬化和肝细胞癌 (HCC) 等晚期肝脏疾病。HCV 感染仅限于肝脏，更具体地说是肝细胞，约占肝细胞的 80%。自 30 年前发现病毒以来，人们对 HCV 进入人类肝细胞的机制进行了广泛的研究。进入机制是一个多步骤过程，依赖于多种宿主因子，包括硫酸乙酰肝素蛋白聚糖 (HSPG)、低密度脂蛋白受体 (LDLR)、四跨膜蛋白 CD81、清道夫受体 B 型 I (SR-BI)、表皮生长因子受体 ( EGFR) 和 Niemann-Pick C1 样 1 (NPC1L1)。此外，为了确定持续感染，HCV 进入取决于紧密连接 (TJ) 蛋白 Claudin-1 (CLDN1) 和 Occludin (OCLN) 的存在。在肝脏中，紧密连接蛋白在结构和稳态中发挥作用，包括密封相邻细胞的顶极以形成胆小管，并分离由正弦血流排出的基底外侧区域。在这篇综述中，我们将重点介绍肝脏紧密连接蛋白在 HCV 感染中的作用，并讨论改善病毒根除的潜在靶向治疗方法。