Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike.

TitleAntibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike.
Publication TypeJournal Article
Year of Publication2015
AuthorsLee J H, Leaman DP, Kim AS, de la Peña ATorrents, Sliepen K, Yasmeen A, Derking R, Ramos A, de Taeye SW, Ozorowski G, Klein F, Burton DR, Nussenzweig MC, Poignard P, Moore JP, Klasse P J, Sanders RW, Zwick MB, Wilson IA, Ward AB
JournalNat Commun
Volume6
Pagination8167
Date Published09/25/2015
ISSN2041-1723
Abstract

The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120-gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. By using biochemical, biophysical and computational methods, we map the previously unknown trimer epitopes of two related antibodies, 3BC315 and 3BC176. A cryo-EM reconstruction of a soluble Env trimer bound to 3BC315 Fab at 9.3 Å resolution reveals that the antibody binds between two gp41 protomers, and neutralizes the virus by accelerating trimer decay. In contrast, bnAb 35O22 binding to a partially overlapping quaternary epitope at the gp120-gp41 interface does not induce decay. A conserved gp41-proximal glycan at N88 was also shown to play a role in the binding kinetics of 3BC176 and 3BC315. Finally, our data suggest that the dynamic structure of the Env trimer influences exposure of bnAb epitopes.

DOI10.1038/ncomms9167
Alternate JournalNat Commun
PubMed ID26404402
PubMed Central IDPMC4586043
Grant ListP01 AI082362 / AI / NIAID NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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