Cryo-electron microscopy and three-dimensional reconstructions of hepatitis C virus particles

Xuekui Yu, Ming Qiao, Ivo Atanasov, Zongyi Hu, Takanobu Kato, T. Jake Liang, Z. Hong Zhou

Research output: Contribution to journalArticlepeer-review

Abstract

The structural details of hepatitis C virus (HCV) have been elusive because of the lack of a robust tissue culture system for producing an adequate amount of virions from infectious sources for in-depth three-dimensional (3D) structural analysis. Using both negative-stain and cryo-electron microscopy (cryoEM), we show that HCV virions isolated from cell culture have a rather uniform size of 500 Å in diameter and that recombinantly expressed HCV-like particles (HCV-LPs) have similar morphologic, biophysical and antigenic features in spite of the varying sizes of the particles. 3D reconstructions were obtained from HCV-LPs with the same size as the HCV virions in the presence and absence of monoclonal antibodies bound to the E1 glycoprotein. The 3D reconstruction of HCV-LP reveals a multilayered architecture, with smooth outer-layer densities arranged in a 'fishbone' configuration. Reconstruction of the particles in complex with anti-E1 antibodies shows that sites of the E1 epitope are exposed and surround the 5-, 3- and 2-fold axes. The binding pattern of the anti-E1 antibody and the fitting of the structure of the dengue virus E glycoprotein into our 3D reconstructions further suggest that the HCV-LP E1 and E2 proteins form a tetramer (or dimer of heterodimers) that corresponds morphologically and functionally to the flavivirus E homodimer. This first 3D structural analysis of HCV particles offers important insights into the elusive mechanisms of HCV assembly and maturation.

Original languageEnglish (US)
Pages (from-to)126-134
Number of pages9
JournalVirology
Volume367
Issue number1
DOIs
StatePublished - Oct 10 2007
Externally publishedYes

Keywords

  • Assembly
  • Envelope protein
  • Neutralizing antibodies
  • Nucleocapsid
  • Viral infection

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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