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Journal of Virology, May 2005, p. 5616-5624, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5616-5624.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

An Unrelated Monoclonal Antibody Neutralizes Human Immunodeficiency Virus Type 1 by Binding to an Artificial Epitope Engineered in a Functionally Neutral Region of the Viral Envelope Glycoproteins

Xinping Ren,1,2 Joseph Sodroski,1,2,3 and Xinzhen Yang1,2*

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute,1 Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115,2 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 021153

Received 31 August 2004/ Accepted 14 December 2004

Neutralizing antibodies often recognize regions of viral envelope glycoproteins that play a role in receptor binding or other aspects of virus entry. To address whether this is a necessary feature of a neutralizing antibody, we identified the V4 region of the gp120 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) as a sequence that is tolerant of drastic change and thus appears to play a negligible role in envelope glycoprotein function. An artificial epitope tag was inserted into the V4 region without a significant effect on virus entry or neutralization by antibodies that recognize HIV-1 envelope glycoprotein sequences. An antibody directed against the artificial epitope tag was able to neutralize the modified, but not the wild-type, HIV-1. Thus, the specific target of a neutralizing antibody need not contribute functionally to the process of virus entry.

* Corresponding author. Mailing address: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115. Phone: (617) 632-4359. Fax: (617) 632-3113. E-mail: xinzhen_yang{at}dfci.harvard.edu.

Journal of Virology, May 2005, p. 5616-5624, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5616-5624.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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