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Journal of Virology, March 2005, p. 3500-3508, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3500-3508.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1

Xinzhen Yang,1,2* Svetla Kurteva,1 Sandra Lee,3,4 and Joseph Sodroski1,2,5

Department of Cancer Immunology and AIDS,1 Department of Biostatistical Science, Dana-Farber Cancer Institute,3 Department of Pathology, Division of AIDS, Harvard Medical School,2 Department of Biostatistics,4 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts5

Received 14 July 2004/ Accepted 3 November 2004

The human immunodeficiency virus envelope glycoproteins function as trimers on the viral surface, where they are targeted by neutralizing antibodies. Different monoclonal antibodies neutralize human immunodeficiency virus type 1 (HIV-1) infectivity by binding to structurally and functionally distinct moieties on the envelope glycoprotein trimer. By measuring antibody neutralization of viruses with mixtures of neutralization-sensitive and neutralization-resistant envelope glycoproteins, we demonstrate that the HIV-1 envelope glycoprotein trimer is inactivated by the binding of a single antibody molecule. Virus neutralization requires essentially all of the functional trimers to be occupied by at least one antibody. This model applies to antibodies differing in neutralizing potency and to virus isolates with various neutralization sensitivities. Understanding these requirements for HIV-1 neutralization by antibodies will assist in establishing goals for an effective AIDS vaccine.

* Corresponding author. Mailing address: Dana-Farber Cancer Institute, JFB-609, 44 Binney St., Boston, MA 02115. Phone: (617) 632-4359. Fax: (617) 632-3113. E-mail: Xinzhen_Yang{at}dfci.harvard.edu.

Journal of Virology, March 2005, p. 3500-3508, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3500-3508.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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