研究人员表示，丙型肝炎病毒（HCV）感染是导致人类慢性肝病、肝硬化和肝细胞癌的主要原因，全世界有超过5800万人受到影响。HCV包膜E1和E2糖蛋白是病毒进入的关键，并构成了中和抗体反应的主要抗原目标。E1E2组装的分子机制，以及E1E2异构体如何结合广泛的中和抗体，仍然难以捉摸。
研究人员展示了膜提取的全长E1E2异构体与三种广义中和抗体（AR4A、AT1209和IGH505）的冷冻电镜结构，其分辨率约为3.5埃。研究人员解析了E1和E2外延域之间的界面，为合理设计疫苗免疫原和抗病毒药物提供了蓝图。
附：英文原文
Title: Structure of the hepatitis C virus E1E2 glycoprotein complex
Author: Alba Torrents de la Pea, Kwinten Sliepen, Lisa Eshun-Wilson, Maddy L. Newby, Joel D. Allen, Ian Zon, Sylvie Koekkoek, Ana Chumbe, Max Crispin, Janke Schinkel, Gabriel C. Lander, Rogier W. Sanders, Andrew B. Ward
Issue&Volume: 2022-10-21
Abstract: Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma in humans and afflicts more than 58 million people worldwide. The HCV envelope E1 and E2 glycoproteins are essential for viral entry and comprise the primary antigenic target for neutralizing antibody responses. The molecular mechanisms of E1E2 assembly, as well as how the E1E2 heterodimer binds broadly neutralizing antibodies, remain elusive. Here, we present the cryo–electron microscopy structure of the membrane-extracted full-length E1E2 heterodimer in complex with three broadly neutralizing antibodies—AR4A, AT1209, and IGH505—at ~3.5-angstrom resolution. We resolve the interface between the E1 and E2 ectodomains and deliver a blueprint for the rational design of vaccine immunogens and antiviral drugs.
DOI: abn9884
Source: https://www.science.org/doi/10.1126/science.abn9884