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Journal of Virology, March 2001, p. 2235-2245, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2235-2245.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Antibody-Mediated Neutralization of Primary Human Immunodeficiency Virus Type 1 Isolates: Investigation of the Mechanism of Inhibition

Catherine Spenlehauer,dagger André Kirn, Anne-Marie Aubertin, and Christiane Moog*

INSERM U74, Institut de Virologie, 67000 Strasbourg, France

Received 8 May 2000/Accepted 22 November 2000

Human immunodeficiency virus type 1 (HIV-1) neutralization occurs when specific antibodies, mainly those directed against the envelope glycoproteins, inhibit infection, most frequently by preventing the entry of the virus into target cells. However, the precise mechanisms of neutralization remain unclear. Previous studies, mostly with cell lines, have produced conflicting results involving either the inhibition of virus attachment or interference with postbinding events. In this study, we investigated the mechanisms of neutralization by immune sera and compared the inhibition of peripheral blood mononuclear cells (PBMC) infection by HIV-1 primary isolates (PI) with the inhibition of T-cell line infection by T-cell line-adapted (TCLA) strains. We followed the kinetics of neutralization to determine at which step of the viral cycle the antibodies act. We found that neutralization of the TCLA strain HIV-1MN/MT-4 required an interaction between antibodies and cell-free virions before the addition of MT-4 cells, whereas PI were neutralized even after adsorption onto PBMC. In addition, the dose-dependent inhibition of HIV-1MN binding to MT-4 cells was strongly correlated with serum-induced neutralization. In contrast, neutralizing sera did not reduce the adhesion of PI to PBMC. Postbinding inhibition was also detected for HIV-1MN produced by and infecting PBMC, demonstrating that the mechanism of neutralization depends on the target cell used in the assay. Finally, we considered whether the different mechanisms of neutralization may reflect the recognition of qualitatively different epitopes on the surface of PI and HIV-1MN or whether they reflect differences in virus attachment to PBMC and MT-4 cells.

* Corresponding author. Mailing address: INSERM U74, Institut de Virologie, 3 rue Koeberlé, 67000 Strasbourg, France. Phone: (33)-(0)3-88-56-63-00. Fax: (33)-(0)3-88-56-63-03. E-mail: c.moog{at}viro-ulp.utrasbg.fr.

dagger Present address: Weill Medical College of Cornell University, Department of Microbiology and Immunology, New York, NY 10021.

Journal of Virology, March 2001, p. 2235-2245, Vol. 75, No. 5
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.5.2235-2245.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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