A prominent site of antibody vulnerability on HIV envelope incorporates a motif associated with CCR5 binding and its camouflaging glycans

Devin Sok, Matthias Pauthner, Bryan Briney, Jeong Hyun Lee, Karen L. Saye-Francisco, Jessica Hsueh, Alejjandra Ramos, Khoa M. Le, Meaghan Jones, Joseph G. Jardine, Raiza Bastidas, Anita Sarkar, Chi-Hui Liang, Sachin S. Shivatare, Chung-yi Wu, William R. Schief, Chi-Huey Wong, Ian A. Wilson, Andrew B. Ward, Jiang Zhu, Pascal Poignard, Dennis R. Burton
Immunity  2016 45:31-45


The dense patch of high-mannose-type glycans surrounding the N332 glycan on the HIV envelope glycoprotein (Env) is targeted by multiple broadly neutralizing antibodies (bnAbs). This region is relatively conserved, implying functional importance, the origins of which are not well understood. Here we describe the isolation of new bnAbs targeting this region. Examination of these and previously described antibodies to Env revealed that four different bnAb families targeted the 324GDIR327 peptide stretch at the base of the gp120 V3 loop and its nearby glycans. We found that this peptide stretch constitutes part of the CCR5 co-receptor binding site, with the high-mannose patch glycans serving to camouflage it from most antibodies. GDIR-glycan bnAbs, in contrast, bound both 324GDIR327 peptide residues and high-mannose patch glycans, which enabled broad reactivity against diverse HIV isolates. Thus, as for the CD4 binding site, bnAb effectiveness relies on circumventing the defenses of a critical functional region on Env.


Technology Platform

Next-Generation Sequencing

Research Topics

B cell Repertoire Analysis

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