Université de Lyon, INSERM and Ecole Normale Supérieure de Lyon, Lyon, France.
Expert Rev Mol Med. 2011 Apr 14;13:e13. doi: 10.1017/S1462399411001785.
Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease worldwide and represents a major public health problem. Viral attachment and entry - the first encounter of the virus with the host cell - are major targets of neutralising immune responses. Thus, a detailed understanding of the HCV entry process offers interesting opportunities for the development of novel therapeutic strategies. Different cellular or soluble host factors mediate HCV entry, and considerable progress has been made in recent years to decipher how they induce HCV attachment, internalisation and membrane fusion. Among these factors, the scavenger receptor class B type I (SR-BI/SCARB1) is essential for HCV replication in vitro, through its interaction with the HCV E1E2 surface glycoproteins and, more particularly, the HVR1 segment located in the E2 protein. SR-BI is an interesting receptor because HCV, whose replication cycle intersects with lipoprotein metabolism, seems to exploit some aspects of its physiological functions, such as cholesterol transfer from high-density lipoprotein (HDL), during cell entry. SR-BI is also involved in neutralisation attenuation and therefore could be an important target for therapeutic intervention. Recent results suggest that it should be possible to identify inhibitors of the interaction of HCV with SR-BI that do not impair its important physiological properties, as discussed in this review.
丙型肝炎病毒（HCV）感染是全球慢性肝病的主要病因，也是一个主要的公共卫生问题。病毒附着和进入——病毒与宿主细胞的第一次接触——是中和免疫反应的主要靶点。因此，深入了解 HCV 进入过程为开发新的治疗策略提供了有趣的机会。不同的细胞或可溶性宿主因子介导 HCV 的进入，近年来在解析它们如何诱导 HCV 附着、内化和膜融合方面取得了相当大的进展。在这些因素中，清道夫受体 B 类 I（SR-BI/SCARB1）通过与 HCV E1E2 表面糖蛋白相互作用，特别是与 E2 蛋白中的 HVR1 片段相互作用，对 HCV 在体外的复制至关重要。SR-BI 是一个有趣的受体，因为 HCV 的复制周期与脂蛋白代谢交叉，它似乎利用了其生理功能的某些方面，例如从高密度脂蛋白（HDL）中转移胆固醇，在细胞进入过程中。SR-BI 还参与中和衰减，因此可能是治疗干预的重要靶点。正如本文所讨论的，最近的结果表明，有可能识别出不损害其重要生理特性的 HCV 与 SR-BI 相互作用的抑制剂。
