Tong Yimin, Lavillette Dimitri, Li Qingchao, Zhong Jin
Unit of Viral Hepatitis, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Unit of Interspecies Transmission of Arboviruses and Antivirals, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Front Immunol. 2018 Jun 19;9:1411. doi: 10.3389/fimmu.2018.01411. eCollection 2018.
Hepatitis C virus (HCV) glycoproteins E1 and E2 form a heterodimer to constitute viral envelope proteins, which play an essential role in virus entry. E1 does not directly interact with host receptors, and its functions in viral entry are exerted mostly through its interaction with E2 that directly binds the receptors. HCV enters the host cell receptor-mediated endocytosis during which the fusion of viral and host endosomal membranes occurs to release viral genome to cytoplasm. A putative fusion peptide in E1 has been proposed to participate in membrane fusion, but its exact role and underlying molecular mechanisms remain to be deciphered. Recently solved crystal structures of the E2 ectodomains and N-terminal of E1 fail to reveal a classical fusion-like structure in HCV envelope glycoproteins. In addition, accumulating evidence suggests that E1 also plays an important role in virus assembly. In this mini-review, we summarize current knowledge on HCV E1 including its structure and biological functions in virus entry, fusion, and assembly, which may provide clues for developing HCV vaccines and more effective antivirals.
丙型肝炎病毒（HCV）糖蛋白E1和E2形成异二聚体以构成病毒包膜蛋白，这些蛋白在病毒进入过程中发挥着至关重要的作用。E1不直接与宿主受体相互作用，其在病毒进入过程中的功能主要通过与直接结合受体的E2相互作用来发挥。HCV通过受体介导的内吞作用进入宿主细胞，在此过程中病毒和宿主内体膜发生融合，从而将病毒基因组释放到细胞质中。有人提出E1中的一个假定融合肽参与膜融合，但其确切作用和潜在分子机制仍有待阐明。最近解析的E2胞外域和E1 N端的晶体结构未能揭示HCV包膜糖蛋白中典型的类似融合的结构。此外，越来越多的证据表明E1在病毒组装中也起着重要作用。在这篇小型综述中，我们总结了目前关于HCV E1的知识，包括其在病毒进入、融合和组装中的结构和生物学功能，这可能为开发HCV疫苗和更有效的抗病毒药物提供线索。
