RT Journal Article
SR Electronic
T1 Networks of HIV-1 envelope glycans maintain antibody epitopes in the face of glycan additions and deletions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.21.959981
DO 10.1101/2020.02.21.959981
A1 Gemma E. Seabright
A1 Christopher A. Cottrell
A1 Marit J. van Gils
A1 Alessio D’addabbo
A1 David J. Harvey
A1 Anna-Janina Behrens
A1 Joel D. Allen
A1 Yasunori Watanabe
A1 Allison Maker
A1 Snezana Vasiljevic
A1 Natalia de Val
A1 Rogier W. Sanders
A1 Andrew B. Ward
A1 Max Crispin
YR 2020
UL http://biorxiv.org/content/early/2020/02/23/2020.02.21.959981.abstract
AB Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike. Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans. Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets. Using cryo-electron microscopy and site-specific glycan analysis, we reveal the hierarchy of importance of glycans in the formation of the 2G12 bnAb epitope, and show that the epitope is only subtly impacted by variations in the glycan network. In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans. Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.