Global and local envelope protein dynamics of hepatitis C virus determine broad antibody sensitivity

Elias H. Augestad, Matteo Castelli, Nicola Clementi, Luisa J. Ströh, Thomas Krey, Roberto Burioni, Nicasio Mancini, Jens Bukh, Jannick Prentoe*

*Corresponding author for this work
11 Citations (Scopus)


Broad antibody sensitivity differences of hepatitis C virus (HCV) isolates and their ability to persist in the presence of neutralizing antibodies (NAbs) remain poorly understood. Here, we show that polymorphisms within glycoprotein E2, including hypervariable region 1 (HVR1) and antigenic site 412 (AS412), broadly affect NAb sensitivity by shifting global envelope protein conformation dynamics between theoretical "closed,"neutralization-resistant and "open,"neutralization-sensitive states. The conformational space of AS412 was skewed toward β-hairpin-like conformations in closed states, which also depended on HVR1, assigning function to these enigmatic E2 regions. Scavenger receptor class B, type I entry dependency of HCV was associated with NAb resistance and correlated perfectly with decreased virus propensity to interact with HCV co-receptor CD81, indicating that decreased NAb sensitivity resulted in a more complex entry pathway. This link between global E1/E2 states and functionally distinct AS412 conformations has important implications for targeting AS412 in rational HCV vaccine designs.

Original languageEnglish
Article numbereabb5938
JournalScience Advances
Issue number35
Publication statusPublished - 08.2020


Dive into the research topics of 'Global and local envelope protein dynamics of hepatitis C virus determine broad antibody sensitivity'. Together they form a unique fingerprint.

Cite this