A Prominent Site of Antibody Vulnerability on HIV Envelope Incorporates a Motif Associated with CCR5 Binding and Its Camouflaging Glycans.

TitleA Prominent Site of Antibody Vulnerability on HIV Envelope Incorporates a Motif Associated with CCR5 Binding and Its Camouflaging Glycans.
Publication TypeJournal Article
Year of Publication2016
AuthorsSok D, Pauthner M, Briney B, Lee J H, Saye-Francisco KL, Hsueh J, Ramos A, Le KM, Jones M, Jardine JG, Bastidas R, Sarkar A, Liang C-H, Shivatare SS, Wu C-Y, Schief WR, Wong C-H, Wilson IA, Ward AB, Zhu J, Poignard P, Burton DR
JournalImmunity
Volume45
Issue1
Pagination31-45
Date Published07/19/2016
ISSN1097-4180
Abstract

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 (324)GDIR(327) 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 (324)GDIR(327) 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.

DOI10.1016/j.immuni.2016.06.026
Alternate JournalImmunity
PubMed ID27438765
Grant ListR37 AI033292 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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