Fusion Peptide of HIV-1 As a Site of Vulnerability to Neutralizing Antibody

Overview

Journal Science

Specialty Science

Date 2016 May 14

PMID 27174988

Citations 225

Authors

Rui Kong

Kai Xu

Tongqing Zhou

Priyamvada Acharya

Thomas Lemmin

Kevin Liu

Gabriel Ozorowski

Cinque Soto

Justin D Taft

Robert T Bailer

Evan M Cale

Lei Chen

Chang W Choi

Gwo-Yu Chuang

Nicole A Doria-Rose

Aliaksandr Druz

Ivelin S Georgiev

Jason Gorman

Jinghe Huang

M Gordon Joyce

Mark K Louder

Xiaochu Ma

Krisha McKee

Sijy ODell

Marie Pancera

Yongping Yang

Scott C Blanchard

Walther Mothes

Dennis R Burton

Wayne C Koff

Mark Connors

Andrew B Ward

Peter D Kwong

John R Mascola

Affiliations

Soon will be listed here.

Abstract

The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. Here, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showed that the N-terminal portion of the fusion peptide can be solvent-exposed. These results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.

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