Structure of the hepatitis C virus E1E2 glycoprotein complex

Science. 2022 Oct 21;378(6617):263-269. doi: 10.1126/science.abn9884. Epub 2022 Oct 20.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Broadly Neutralizing Antibodies
  • Cryoelectron Microscopy
  • Hepacivirus* / chemistry
  • Hepacivirus* / immunology
  • Hepatitis C* / virology
  • Humans
  • Protein Multimerization
  • Viral Envelope Proteins* / chemistry
  • Viral Envelope Proteins* / immunology
  • Viral Hepatitis Vaccines / chemistry
  • Viral Hepatitis Vaccines / immunology

Substances

  • Antiviral Agents
  • Broadly Neutralizing Antibodies
  • Viral Envelope Proteins
  • E1 protein, Hepatitis C virus
  • glycoprotein E2, Hepatitis C virus
  • Viral Hepatitis Vaccines