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Journal of Virology, March 2004, p. 2394-2404, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2394-2404.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The V3 Loop Is Accessible on the Surface of Most Human Immunodeficiency Virus Type 1 Primary Isolates and Serves as a Neutralization Epitope

Miroslaw K. Gorny,1 Kathy Revesz,2 Constance Williams,1 Barbara Volsky,1 Mark K. Louder,3 Christopher A. Anyangwe,4 Chavdar Krachmarov,5 Samuel C. Kayman,5 Abraham Pinter,5 Arthur Nadas,6 Phillipe N. Nyambi,1,2 John R. Mascola,3 and Susan Zolla-Pazner1,2*

Department of Pathology,1 Institute of Environmental Medicine, New York University School of Medicine, New York, New York 10016,6 Research Enhancement Award Program, Veterans Affairs New York Harbor Healthcare System, New York, New York 10010,2 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,3 Alpha Royal Clinic, Bamenda, Cameroon,4 Laboratory of Retroviral Biology, Public Health Research Institute, Newark, New Jersey 071035

Received 1 August 2003/ Accepted 14 November 2003

Antibodies (Abs) against the V3 loop of the human immunodeficiency virus type 1 gp120 envelope glycoprotein were initially considered to mediate only type-specific neutralization of T-cell-line-adapted viruses. However, recent data show that cross-neutralizing V3 Abs also exist, and primary isolates can be efficiently neutralized with anti-V3 monoclonal Abs (MAbs). The neutralizing activities of anti-V3 polyclonal Abs and MAbs may, however, be limited due to antigenic variations of the V3 region, a lack of V3 exposure on the surface of intact virions, or Ab specificity. For clarification of this issue, a panel of 32 human anti-V3 MAbs were screened for neutralization of an SF162-pseudotyped virus in a luciferase assay. MAbs selected with a V3 fusion protein whose V3 region mimics the conformation of the native virus were significantly more potent than MAbs selected with V3 peptides. Seven MAbs were further tested for neutralizing activity against 13 clade B viruses in a single-round peripheral blood mononuclear cell assay. While there was a spectrum of virus sensitivities to the anti-V3 MAbs observed, 12 of the 13 viruses were neutralized by one or more of the anti-V3 MAbs. MAb binding to intact virions correlated significantly with binding to solubilized gp120s and with the potency of neutralization. These results demonstrate that the V3 loop is accessible on the native virus envelope, that the strength of binding of anti-V3 Abs correlates with the potency of neutralization, that V3 epitopes may be shared rather than type specific, and that Abs against the V3 loop, particularly those targeting conformational epitopes, can mediate the neutralization of primary isolates.

* Corresponding author. Mailing address: Veterans Affairs Medical Center, 423 E. 23rd St., Room 18124N, New York, NY 10010. Phone: (212) 263-6769. Fax: (212) 951-6321. E-mail: zollas01{at}endeavor.med.nyu.edu.

Journal of Virology, March 2004, p. 2394-2404, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2394-2404.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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