Hepatitis C virus envelope protein dynamics and the link to hypervariable region 1


Conformational dynamics of viral envelope proteins seem to be involved in mediating evasion from neutralizing antibodies (NAbs) by mechanisms that limit exposure of conserved protein motifs. For hepatitis C virus (HCV), molecular studies have only recently begun to unveil how such dynamics of the envelope protein heterodimer, E1/E2, are linked to viral entry and NAb evasion. Here, we review data suggesting that E1/E2 exists in an equilibrium between theoretical 'open' (NAb-sensitive) and 'closed' (NAb-resistant) conformational states. We describe how this equilibrium is influenced by viral sequence polymorphisms and that it is critically dependent on the N-terminal region of E2, termed hypervariable region 1 (HVR1). Finally, we discuss how it appears that the virus binding site for the HCV entry co-receptor CD81 is less available in 'closed' E1/E2 states and that NAb-resistant viruses require a more intricate entry pathway involving also the entry co-receptor, SR-BI.

Original languageEnglish
JournalCurrent opinion in virology
Pages (from-to)69-75
Number of pages7
Publication statusPublished - Oct 2021


  • Antibodies, Neutralizing
  • Hepacivirus/genetics
  • Hepatitis C
  • Humans
  • Viral Envelope Proteins/genetics
  • Virus Internalization


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