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Journal of Virology, August 2009, p. 7397-7410, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00656-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Utilization of Immunoglobulin G Fc Receptors by Human Immunodeficiency Virus Type 1: a Specific Role for Antibodies against the Membrane-Proximal External Region of gp41

Lautaro G. Perez,¹ Matthew R. Costa,¹ Christopher A. Todd,¹ Barton F. Haynes,² and David C. Montefiori^1*

Departments of Surgery,¹ Medicine, Duke University Medical Center, Durham, North Carolina 27710²

Received 30 March 2009/ Accepted 11 May 2009

Receptors (FcRs) for the constant region of immunoglobulin G (IgG) are an important link between humoral immunity and cellular immunity. To help define the role of FcRs in determining the fate of human immunodeficiency virus type 1 (HIV-1) immune complexes, cDNAs for the four major human Fc receptors (FcRI, FcRIIa, FcRIIb, and FcRIIIa) were stably expressed by lentiviral transduction in a cell line (TZM-bl) commonly used for standardized assessments of HIV-1 neutralization. Individual cell lines, each expressing a different FcR, bound human IgG, as evidence that the physical properties of the receptors were preserved. In assays with a HIV-1 multisubtype panel, the neutralizing activities of two monoclonal antibodies (2F5 and 4E10) that target the membrane-proximal external region (MPER) of gp41 were potentiated by FcRI and, to a lesser extent, by FcRIIb. Moreover, the neutralizing activity of an HIV-1-positive plasma sample known to contain gp41 MPER-specific antibodies was potentiated by FcRI. The neutralizing activities of monoclonal antibodies b12 and 2G12 and other HIV-1-positive plasma samples were rarely affected by any of the four FcRs. Effects with gp41 MPER-specific antibodies were moderately stronger for IgG1 than for IgG3 and were ineffective for Fab. We conclude that FcRI and FcRIIb facilitate antibody-mediated neutralization of HIV-1 by a mechanism that is dependent on the Fc region, IgG subclass, and epitope specificity of antibody. The FcR effects seen here suggests that the MPER of gp41 could have greater value for vaccines than previously recognized.

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* Corresponding author. Mailing address: Department of Surgery, Laboratory for AIDS Vaccine Research and Development, P.O. Box 2926, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-5278. Fax: (919) 684-4288. E-mail: monte{at}duke.edu

Published ahead of print on 20 May 2009.

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Journal of Virology, August 2009, p. 7397-7410, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00656-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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