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Review
. 2008 Mar;72(1):54-84, table of contents.
doi: 10.1128/MMBR.00020-07.

The membrane-proximal external region of the human immunodeficiency virus type 1 envelope: dominant site of antibody neutralization and target for vaccine design

Marinieve Montero  1 , Nienke E van Houten, Xin Wang, Jamie K Scott
Affiliations
Review

The membrane-proximal external region of the human immunodeficiency virus type 1 envelope: dominant site of antibody neutralization and target for vaccine design

Marinieve Montero et al. Microbiol Mol Biol Rev. 2008 Mar.

Abstract

Enormous efforts have been made to produce a protective vaccine against human immunodeficiency virus type 1; there has been little success. However, the identification of broadly neutralizing antibodies against epitopes on the highly conserved membrane-proximal external region (MPER) of the gp41 envelope protein has delineated this region as an attractive vaccine target. Furthermore, emerging structural information on the MPER has provided vaccine designers with new insights for building relevant immunogens. This review describes the current state of the field regarding (i) the structure and function of the gp41 MPER; (ii) the structure and binding mechanisms of the broadly neutralizing antibodies 2F5, 4E10, and Z13; and (iii) the development of an MPER-targeting vaccine. In addition, emerging approaches to vaccine design are presented.

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Figures

FIG. 1.
FIG. 1.
Schematic representation of the gp41 domains.
FIG. 2.
FIG. 2.
The flexibility of the MPER is revealed by the differences in its structure. (A) NMR spectroscopy structure of the MPER peptide (KWASLWNWFNITNWYIK) in DPC micelles. (Top) Side view with the exposed face oriented toward the top of the figure. (Bottom) End view. (Reprinted with permission from reference . Copyright © 2001 American Chemical Society.) (B) Crystal structure of the 2F5 epitope peptide (EKNEQELLELDKWASLW) (yellow) in complex with the 2F5 Fab (not shown). This figure was made using DeepView Swiss-PDB Viewer from PDB coordinates (PDB accession number 1TJI) described previously (170). (C) Crystal structure of Fab 4E10 in complex with its epitope peptide (GWNWFDITNWGK) (yellow). The light chain is shown in red, and the heavy chain is shown in blue. This figure was made using DeepView Swiss-PDB Viewer from PDB coordinates (PDB accession number 1TZG) described previously (38). (D) Hypothetical model of the MPER (DKWASLWNWFDITNWLW) as described by Nelson et al. (164). (Reprinted from reference with permission.)
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