Structural perspectives on HCV humoral immune evasion mechanisms

Curr Opin Virol. 2021 Aug;49:92-101. doi: 10.1016/j.coviro.2021.05.002. Epub 2021 Jun 3.


The molecular mechanisms of hepatitis C virus (HCV) persistence and pathogenesis are poorly understood. The design of an effective HCV vaccine is challenging despite a robust humoral immune response against closely related strains of HCV. This is primarily because of the huge genetic diversity of HCV and the molecular evolution of various virus escape mechanisms. These mechanisms are steered by the presence of a high mutational rate in HCV, structural plasticity of the immunodominant regions on the virion surface of diverse HCV genotypes, and constant amino acid substitutions on key structural components of HCV envelope glycoproteins. Here, we review the molecular basis of neutralizing antibody (nAb)-mediated immune response against diverse HCV variants, HCV-steered humoral immune evasion strategies and explore the essential structural elements to consider for designing a universal HCV vaccine. Structural perspectives on key escape pathways mediated by a point mutation within the epitope, allosteric modulation of the epitope by distant mutations and glycan shift on envelope glycoproteins will be highlighted (abstract graphic).

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Antigens, Viral / chemistry
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Epitopes
  • Genetic Variation
  • Hepacivirus / chemistry
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis C Antibodies / immunology
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Immune Evasion*
  • Immunity, Humoral
  • Immunodominant Epitopes
  • Mutation
  • Protein Conformation
  • Protein Domains
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*


  • Antibodies, Neutralizing
  • Antigens, Viral
  • E1 protein, Hepatitis C virus
  • Epitopes
  • Hepatitis C Antibodies
  • Immunodominant Epitopes
  • Viral Envelope Proteins
  • glycoprotein E2, Hepatitis C virus