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 Blanco, J.
Right arrow Articles by Esté, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blanco, J.
Right arrow Articles by Esté, J. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2000, p. 51-56, Vol. 44, No. 1
0066-4804/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The CXCR4 Antagonist AMD3100 Efficiently Inhibits Cell-Surface-Expressed Human Immunodeficiency Virus Type 1 Envelope-Induced Apoptosis

Julià Blanco,1,* Jordi Barretina,1 Geoffrey Henson,2 Gary Bridger,2 Erik De Clercq,3 Bonaventura Clotet,1 and José A. Esté1

Institut de Recerca de la SIDA-Caixa, Laboratori de Retrovirologia, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Catalonia, Spain1; AnorMED Inc., Langley, British Columbia V2Y1 N5, Canada2; and Rega Institute for Medical Research, B 3000 Leuven, Belgium3

Received 12 March 1999/Returned for modification 20 July 1999/Accepted 18 October 1999

Infection by human immunodeficiency virus type 1 (HIV-1) has been associated with increased cell death by apoptosis in infected and uninfected cells. The envelope glycoprotein complex ([gp120/gp41]n) of X4 HIV-1 isolates is involved in both infected and uninfected cell death via its interaction with cellular receptors CD4 and CXCR4. We studied the effect of the blockade of CXCR4 receptors by the agonist stromal derived factor (SDF-1alpha ) and the antagonist bicyclam AMD3100 on apoptotic cell death of CD4+ cells in different models of HIV infection. In HIV-infected CEM or SUP-T1 cultures, AMD3100 showed antiapoptotic activity even when added 24 h after infection. In contrast, other antiviral agents, such as zidovudine, failed to block apoptosis under these conditions. The antiapoptotic activity of AMD3100 was also studied in coculture of peripheral blood mononuclear cells or CD4+ cell lines with chronically infected H9/IIIB cells. AMD3100 was found to inhibit both syncytium formation and apoptosis induction with 50% inhibitory concentrations ranging from 0.009 to 0.24 µg/ml, depending on the cell type. When compared to SDF-1alpha , AMD3100 showed higher inhibitory potency in all cell lines tested. Our data indicate that the bicyclam AMD3100 not only inhibits HIV replication but also efficiently blocks cell-surface-expressed HIV-1 envelope-induced apoptosis in uninfected cells.

* Corresponding author. Mailing address: Fundació irsiCaixa, Laboratori de Retrovirologia, Hospital Universitari Germans Trias i Pujol, Ctra. Del Canyet s/n, 08916 Badalona, Catalonia, Spain. Phone: 34-93-4656374. Fax: 34-93-4653968. E-mail: jblanco{at}ns.hugtip.scs.es.

Antimicrobial Agents and Chemotherapy, January 2000, p. 51-56, Vol. 44, No. 1
0066-4804/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Blanco, J., Barretina, J., Clotet, B., Este, J. A. (2004). R5 HIV gp120-mediated cellular contacts induce the death of single CCR5-expressing CD4 T cells by a gp41-dependent mechanism. J. Leukoc. Biol. 76: 804-811 [Abstract] [Full Text]  
  • Decrion, A.-Z., Varin, A., Estavoyer, J.-M., Herbein, G. (2004). CXCR4-mediated T cell apoptosis in human immunodeficiency virus infection. J. Gen. Virol. 85: 1471-1478 [Abstract] [Full Text]  
  • Misse, D., Esteve, P.-O., Renneboog, B., Vidal, M., Cerutti, M., St Pierre, Y., Yssel, H., Parmentier, M., Veas, F. (2001). HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway. Blood 98: 541-547 [Abstract] [Full Text]  
  • Badley, A. D., Pilon, A. A., Landay, A., Lynch, D. H. (2000). Mechanisms of HIV-associated lymphocyte apoptosis. Blood 96: 2951-2964 [Abstract] [Full Text]  
  • De Clercq, E. (2000). Inhibition of HIV Infection by Bicyclams, Highly Potent and Specific CXCR4 Antagonists. Mol. Pharmacol. 57: 833-839 [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»