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Open Access Short Report

Neutralization of X4- and R5-tropic HIV-1 NL4-3 variants by HOCl-modified serum albumins

Svenja Polzer13, Melanie van Yperen1, Martin Kirst1, Birco Schwalbe1, Heiner Schaal2 and Michael Schreiber1*

Author Affiliations

1 Bernhard-Nocht Institute for Tropical Medicine, Department of Virology, Hamburg, Germany

2 Institute for Virology, Heinrich-Heine-University of Duesseldorf, Germany

3 Current address: Cephalon GmbH, Martinsried, Germany

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BMC Research Notes 2010, 3:155  doi:10.1186/1756-0500-3-155

Published: 2 June 2010

Abstract

Background

Myeloperoxidase (MPO), an important element of the microbicidal activity of neutrophils, generates hypochlorous acid (HOCl) from H2O2 and chloride, which is released into body fluids. Besides its direct microbicidal activity, HOCl can react with amino acid residues and HOCl-modified proteins can be detected in vivo.

Findings

This report is based on binding studies of HOCl-modified serum albumins to HIV-1 gp120 and three different neutralization assays using infectious virus. The binding studies were carried out by surface plasmon resonance spectroscopy and by standard ELISA techniques. Virus neutralization assays were carried out using HIV-1 NL4-3 virus and recombinant strains with CXCR4 and CCR5 coreceptor usage. Viral infection was monitored by a standard p24 or X-gal staining assay. Our data demonstrate that HOCl-modified mouse-, bovine- and human serum albumins all bind to the HIV-1 NL4-3 gp120 (LAV) glycoprotein in contrast to non-modified albumin. Binding of HOCl-modified albumin to gp120 correlated to the blockade of CD4 as well as that of V3 loop specific monoclonal antibody binding. In neutralization experiments, HOCl-modified serum albumins inhibited replication and syncytium formation of the X4- and R5-tropic NL4-3 isolates in a dose dependent manner.

Conclusions

Our data indicate that HOCl-modified serum albumin veils the binding site for CD4 and the V3 loop on gp120. Such masking of the viral gp120/gp41 envelope complex might be a simple but promising strategy to inactivate HIV-1 and therefore prevent infection when HOCl-modified serum albumin is applied, for example, as a topical microbicide.