Wrensch Florian, Crouchet Emilie, Ligat Gaetan, Zeisel Mirjam B, Keck Zhen-Yong, Foung Steven K H, Schuster Catherine, Baumert Thomas F
INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France.
Université de Strasbourg, Strasbourg, France.
Front Immunol. 2018 Jun 21;9:1436. doi: 10.3389/fimmu.2018.01436. eCollection 2018.
With more than 71 million people chronically infected, hepatitis C virus (HCV) is one of the leading causes of liver disease and hepatocellular carcinoma. While efficient antiviral therapies have entered clinical standard of care, the development of a protective vaccine is still elusive. Recent studies have shown that the HCV life cycle is closely linked to lipid metabolism. HCV virions associate with hepatocyte-derived lipoproteins to form infectious hybrid particles that have been termed lipo-viro-particles. The close association with lipoproteins is not only critical for virus entry and assembly but also plays an important role during viral pathogenesis and for viral evasion from neutralizing antibodies. In this review, we summarize recent findings on the functional role of apolipoproteins for HCV entry and assembly. Furthermore, we highlight the impact of HCV-apolipoprotein interactions for evasion from neutralizing antibodies and discuss the consequences for antiviral therapy and vaccine design. Understanding these interactions offers novel strategies for the development of an urgently needed protective vaccine.
丙型肝炎病毒（HCV）慢性感染人数超过7100万，是导致肝病和肝细胞癌的主要原因之一。尽管高效抗病毒疗法已成为临床标准治疗方法，但保护性疫苗的研发仍然难以实现。最近的研究表明，HCV生命周期与脂质代谢密切相关。HCV病毒粒子与肝细胞衍生的脂蛋白结合，形成被称为脂质病毒粒子的传染性杂交颗粒。与脂蛋白的紧密结合不仅对病毒进入和组装至关重要，而且在病毒发病机制以及病毒逃避中和抗体方面也发挥着重要作用。在本综述中，我们总结了载脂蛋白在HCV进入和组装中的功能作用的最新发现。此外，我们强调了HCV-载脂蛋白相互作用对逃避中和抗体的影响，并讨论了其对抗病毒治疗和疫苗设计的影响。了解这些相互作用为开发急需的保护性疫苗提供了新策略。
