This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schønning, K.
Right arrow Articles by Stig Hansen, J.-E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schønning, K.
Right arrow Articles by Stig Hansen, J.-E.

 Previous Article  |  Next Article 

Journal of Virology, October 1999, p. 8364-8370, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Stoichiometry of Monoclonal Antibody Neutralization of T-Cell Line-Adapted Human Immunodeficiency Virus Type 1

Kristian Schønning,1,2,* Ole Lund,1 Ole Søgaard Lund,1 and John-Erik Stig Hansen1

Laboratory for Infectious Diseases 144,1 and Department of Clinical Microbiology 445,2 Hvidovre Hospital, DK-2650 Hvidovre, Denmark

Received 9 November 1998/Accepted 2 July 1999

In order to study the stoichiometry of monoclonal antibody (MAb) neutralization of T-cell line-adapted human immunodeficiency virus type 1 (HIV-1) in antibody excess and under equilibrium conditions, we exploited the ability of HIV-1 to generate mixed oligomers when different env genes are coexpressed. By the coexpression of Env glycoproteins that either can or cannot bind a neutralizing MAb in an env transcomplementation assay, virions were generated in which the proportion of MAb binding sites could be regulated. As the proportion of MAb binding sites in Env chimeric virus increased, MAb neutralization gradually increased. Virus neutralization by virion aggregation was minimal, as MAb binding to HIV-1 Env did not interfere with an AMLV Env-mediated infection by HIV-1(AMLV/HIV-1) pseudotypes of CD4- HEK293 cells. MAb neutralization of chimeric virions could be described as a third-order function of the proportion of Env antigen refractory to MAb binding. This scenario is consistent with the Env oligomer constituting the minimal functional unit and neutralization occurring incrementally as each Env oligomer binds MAb. Alternatively, the data could be fit to a sigmoid function. Thus, these data could not exclude the existence of a threshold for neutralization. However, results from MAb neutralization of chimeric virus containing wild-type Env and Env defective in CD4 binding was readily explained by a model of incremental MAb neutralization. In summary, the data indicate that MAb neutralization of T-cell line-adapted HIV-1 is incremental rather than all or none and that each MAb binding an Env oligomer reduces the likelihood of infection.

* Corresponding author. Mailing address: Department of Clinical Microbiology 445, Hvidovre Hospital, Kettegård Allé 30, DK-2650 Hvidovre, Denmark. Phone: 45 3632 2429. Fax: 45 3632 3357. E-mail: krs{at}dadlnet.dk.

Journal of Virology, October 1999, p. 8364-8370, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Magnus, C., Rusert, P., Bonhoeffer, S., Trkola, A., Regoes, R. R. (2009). Estimating the Stoichiometry of Human Immunodeficiency Virus Entry. J. Virol. 83: 1523-1531 [Abstract] [Full Text]  
  • Ou, W., Silver, J. (2006). Stoichiometry of Murine Leukemia Virus Envelope Protein-Mediated Fusion and Its Neutralization. J. Virol. 80: 11982-11990 [Abstract] [Full Text]  
  • Yang, X., Lipchina, I., Cocklin, S., Chaiken, I., Sodroski, J. (2006). Antibody Binding Is a Dominant Determinant of the Efficiency of Human Immunodeficiency Virus Type 1 Neutralization. J. Virol. 80: 11404-11408 [Abstract] [Full Text]  
  • Yang, X., Kurteva, S., Ren, X., Lee, S., Sodroski, J. (2005). Stoichiometry of Envelope Glycoprotein Trimers in the Entry of Human Immunodeficiency Virus Type 1. J. Virol. 79: 12132-12147 [Abstract] [Full Text]  
  • Yang, X., Kurteva, S., Lee, S., Sodroski, J. (2005). Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1. J. Virol. 79: 3500-3508 [Abstract] [Full Text]  
  • Labrijn, A. F., Poignard, P., Raja, A., Zwick, M. B., Delgado, K., Franti, M., Binley, J., Vivona, V., Grundner, C., Huang, C.-C., Venturi, M., Petropoulos, C. J., Wrin, T., Dimitrov, D. S., Robinson, J., Kwong, P. D., Wyatt, R. T., Sodroski, J., Burton, D. R. (2003). Access of Antibody Molecules to the Conserved Coreceptor Binding Site on Glycoprotein gp120 Is Sterically Restricted on Primary Human Immunodeficiency Virus Type 1. J. Virol. 77: 10557-10565 [Abstract] [Full Text]  
  • Pantophlet, R., Wilson, I. A., Burton, D. R. (2003). Hyperglycosylated Mutants of Human Immunodeficiency Virus (HIV) Type 1 Monomeric gp120 as Novel Antigens for HIV Vaccine Design. J. Virol. 77: 5889-5901 [Abstract] [Full Text]  
  • Poignard, P., Moulard, M., Golez, E., Vivona, V., Franti, M., Venturini, S., Wang, M., Parren, P. W. H. I., Burton, D. R. (2002). Heterogeneity of Envelope Molecules Expressed on Primary Human Immunodeficiency Virus Type 1 Particles as Probed by the Binding of Neutralizing and Nonneutralizing Antibodies. J. Virol. 77: 353-365 [Abstract] [Full Text]  
  • Pantophlet, R., Ollmann Saphire, E., Poignard, P., Parren, P. W. H. I., Wilson, I. A., Burton, D. R. (2002). Fine Mapping of the Interaction of Neutralizing and Nonneutralizing Monoclonal Antibodies with the CD4 Binding Site of Human Immunodeficiency Virus Type 1 gp120. J. Virol. 77: 642-658 [Abstract] [Full Text]  
  • Klasse, P. J., Sattentau, Q. J. (2002). Occupancy and mechanism in antibody-mediated neutralization of animal viruses. J. Gen. Virol. 83: 2091-2108 [Abstract] [Full Text]  
  • Salzwedel, K., Berger, E. A. (2000). Cooperative subunit interactions within the oligomeric envelope glycoprotein of HIV-1: Functional complementation of specific defects in gp120 and gp41. Proc. Natl. Acad. Sci. USA 10.1073/pnas.230438497v1 [Abstract] [Full Text]  
  • Salzwedel, K., Berger, E. A. (2000). Cooperative subunit interactions within the oligomeric envelope glycoprotein of HIV-1: Functional complementation of specific defects in gp120 and gp41. Proc. Natl. Acad. Sci. USA 97: 12794-12799 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»