Research ArticleHIV

Promiscuous Glycan Site Recognition by Antibodies to the High-Mannose Patch of gp120 Broadens Neutralization of HIV

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Science Translational Medicine  14 May 2014:
Vol. 6, Issue 236, pp. 236ra63
DOI: 10.1126/scitranslmed.3008104

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Neutralizing Antibodies with a Sweet Tooth

Sugar can be quite tempting—as anyone who’s seen a kid rip into birthday cake can attest. Yet, antibodies can also have a sweet tooth, targeting glycan modifications on the surface of proteins. Indeed, some antibodies that neutralize multiple HIV strains—broadly neutralizing monoclonal antibodies (bnmAbs)—target a high-mannose patch on the HIV protein Env. Although this high-mannose patch is centered around the glycan at position 332 (N332), it has remained unclear if the N332 glycan is absolutely required for neutralization and, if not, why not. Sok et al. found that these mannose patch–targeting antibodies can bind alternate glycans in the absence of N332, which helps to explain their ability to neutralize many strains of HIV.

Specifically, some bnmAbs can bind to the N334 site when that replaces the N332 site and some can form more interactions with other glycans, particularly complex-type glycans on variable loops, if the N332 sugar is absent. These data also suggest that mannose patch–targeting bnmAbs can work in combination to neutralize a wider range of different strains than single bnmAbs. The promiscuity of glycan binding by these sugar-loving antibodies is important to consider for both vaccine and therapeutic antibody development.

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