Peptides trap the human immunodeficiency virus type 1 envelope glycoprotein fusion intermediate at two sites.

Abstract:

:Human immunodeficiency virus type 1 (HIV-1) entry into target cells requires folding of two heptad-repeat regions (N-HR and C-HR) of gp41 into a trimer of N-HR and C-HR hairpins, which brings viral and target cell membranes together to facilitate membrane fusion. Peptides corresponding to the N-HR and C-HR of gp41 are potent inhibitors of HIV infection. Here we report new findings on the mechanism of inhibition of a N-HR peptide and compare these data with inhibition by a C-HR peptide. Using intact envelope glycoprotein (Env) under fusogenic conditions, we show that the N-HR peptide preferentially binds receptor-activated Env and that CD4 binding is sufficient for triggering conformational changes that allow the peptide to bind Env, results similar to those seen with the C-HR peptide. However, activation by both CD4 and chemokine receptors further enhances Env binding by both peptides. We also show that a nonconservative mutation in the N-HR of gp41 abolishes C-HR peptide but not N-HR peptide binding to gp41. These results indicate that there are two distinct sites in receptor-activated Env that are potential targets for drug or vaccine development.

journal_name

J Virol

journal_title

Journal of virology

authors

He Y,Vassell R,Zaitseva M,Nguyen N,Yang Z,Weng Y,Weiss CD

doi

10.1128/jvi.77.3.1666-1671.2003

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

1666-71

issue

3

eissn

0022-538X

issn

1098-5514

journal_volume

77

pub_type

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