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 Roggero, R.
Right arrow Articles by Biard-Piechaczyk, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Roggero, R.
Right arrow Articles by Biard-Piechaczyk, M.

 Previous Article  |  Next Article 

Journal of Virology, August 2001, p. 7637-7650, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7637-7650.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Binding of Human Immunodeficiency Virus Type 1 gp120 to CXCR4 Induces Mitochondrial Transmembrane Depolarization and Cytochrome c-Mediated Apoptosis Independently of Fas Signaling

Rodolphe Roggero,1 Véronique Robert-Hebmann,1 Steve Harrington,1 Joachim Roland,1 Laurence Vergne,1 Sara Jaleco,2 Christian Devaux,1 and Martine Biard-Piechaczyk1,*

Laboratoire Infections Rétrovirales et Signalisation Cellulaire CNRS EP 2104, Institut de Biologie, 34060 Montpellier Cedex,1 and IGMM, CNRS UMR 5535, IFR24, Montpellier,2 France

Received 10 November 2000/Accepted 14 May 2001

Apoptosis of CD4+ T lymphocytes, induced by contact between human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120) and its receptors, could contribute to the cell depletion observed in HIV-infected individuals. CXCR4 appears to play an important role in gp120-induced cell death, but the mechanisms involved in this apoptotic process remain poorly understood. To get insight into the signal transduction pathways connecting CXCR4 to apoptosis following gp120 binding, we used different cell lines expressing wild-type CXCR4 and a truncated form of CD4 that binds gp120 but lacks the ability to transduce signals. The present study demonstrates that (i) the interaction of cell-associated gp120 with CXCR4-expressing target cells triggers a rapid dissipation of the mitochondrial transmembrane potential resulting in the cytosolic release of cytochrome c from the mitochondria to cytosol, concurrent with activation of caspase-9 and -3; (ii) this apoptotic process is independent of Fas signaling; and (iii) cooperation with a CD4 signal is not required. In addition, following coculture with cells expressing gp120, a Fas-independent apoptosis involving mitochondria and caspase activation is also observed in primary umbilical cord blood CD4+ T lymphocytes expressing high levels of CXCR4. Thus, this gp120-mediated apoptotic pathway may contribute to CD4+ T-cell depletion in AIDS.

* Corresponding author. Mailing address: Laboratoire Infections Rétrovirales et Signalisation Cellulaire CNRS EP 2104, Institut de Biologie, 4 Boulevard Henri IV, 34060 Montpellier Cedex, France. Phone: (33) 4 67 60 86 60. Fax: (33) 4 67 60 44 20. E-mail: piechacz{at}xerxes.crbm.cnrs-mop.fr.

Journal of Virology, August 2001, p. 7637-7650, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7637-7650.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Garg, H., Joshi, A., Freed, E. O., Blumenthal, R. (2007). Site-specific Mutations in HIV-1 gp41 Reveal a Correlation between HIV-1-mediated Bystander Apoptosis and Fusion/Hemifusion. J. Biol. Chem. 282: 16899-16906 [Abstract] [Full Text]  
  • Trushin, S. A., Algeciras-Schimnich, A., Vlahakis, S. R., Bren, G. D., Warren, S., Schnepple, D. J., Badley, A. D. (2007). Glycoprotein 120 Binding to CXCR4 Causes p38-Dependent Primary T Cell Death That Is Facilitated by, but Does Not Require Cell-Associated CD4. J. Immunol. 178: 4846-4853 [Abstract] [Full Text]  
  • Fernando, K., Hu, H., Ni, H., Hoxie, J. A., Weissman, D. (2007). Vaccine-delivered HIV envelope inhibits CD4+ T-cell activation, a mechanism for poor HIV vaccine responses. Blood 109: 2538-2544 [Abstract] [Full Text]  
  • Ji, J., Chen, J. J-Y., Braciale, V. L., Cloyd, M. W. (2007). Apoptosis induced in HIV-1-exposed, resting CD4+ T cells subsequent to signaling through homing receptors is Fas/Fas ligand-mediated. J. Leukoc. Biol. 81: 297-305 [Abstract] [Full Text]  
  • Meissner, E. G., Zhang, L., Jiang, S., Su, L. (2006). Fusion-Induced Apoptosis Contributes to Thymocyte Depletion by a Pathogenic Human Immunodeficiency Virus Type 1 Envelope in the Human Thymus. J. Virol. 80: 11019-11030 [Abstract] [Full Text]  
  • Anand, A. R., Ganju, R. K. (2006). HIV-1 gp120-mediated Apoptosis of T Cells Is Regulated by the Membrane Tyrosine Phosphatase CD45. J. Biol. Chem. 281: 12289-12299 [Abstract] [Full Text]  
  • Melli, G., Keswani, S. C., Fischer, A., Chen, W., Hoke, A. (2006). Spatially distinct and functionally independent mechanisms of axonal degeneration in a model of HIV-associated sensory neuropathy. Brain 129: 1330-1338 [Abstract] [Full Text]  
  • Garg, H., Blumenthal, R. (2006). HIV gp41-induced apoptosis is mediated by caspase-3-dependent mitochondrial depolarization, which is inhibited by HIV protease inhibitor nelfinavir. J. Leukoc. Biol. 79: 351-362 [Abstract] [Full Text]  
  • Perfettini, J.-L., Castedo, M., Nardacci, R., Ciccosanti, F., Boya, P., Roumier, T., Larochette, N., Piacentini, M., Kroemer, G. (2005). Essential role of p53 phosphorylation by p38 MAPK in apoptosis induction by the HIV-1 envelope. JEM 201: 279-289 [Abstract] [Full Text]  
  • Andreau, K., Perfettini, J.-L., Castedo, M., Metivier, D., Scott, V., Pierron, G., Kroemer, G. (2004). Contagious apoptosis facilitated by the HIV-1 envelope: fusion-induced cell-to-cell transmission of a lethal signal. J. Cell Sci. 117: 5643-5653 [Abstract] [Full Text]  
  • Huang, M.-B., Jin, L. L., James, C. O., Khan, M., Powell, M. D., Bond, V. C. (2004). Characterization of Nef-CXCR4 Interactions Important for Apoptosis Induction. J. Virol. 78: 11084-11096 [Abstract] [Full Text]  
  • 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]  
  • Komoto, S., Tsuji, S., Ibrahim, M. S., Li, Y.-G., Warachit, J., Taniguchi, K., Ikuta, K. (2003). The Vpu Protein of Human Immunodeficiency Virus Type 1 Plays a Protective Role against Virus-Induced Apoptosis in Primary CD4+ T Lymphocytes. J. Virol. 77: 10304-10313 [Abstract] [Full Text]  
  • LaBonte, J. A., Madani, N., Sodroski, J. (2003). Cytolysis by CCR5-Using Human Immunodeficiency Virus Type 1 Envelope Glycoproteins Is Dependent on Membrane Fusion and Can Be Inhibited by High Levels of CD4 Expression. J. Virol. 77: 6645-6659 [Abstract] [Full Text]  
  • Twu, C., Liu, N. Q., Popik, W., Bukrinsky, M., Sayre, J., Roberts, J., Rania, S., Bramhandam, V., Roos, K. P., MacLellan, W. R., Fiala, M. (2002). Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion- and death receptor-controlled pathways. Proc. Natl. Acad. Sci. USA 99: 14386-14391 [Abstract] [Full Text]  
  • Bitzer, M., Armeanu, S., Prinz, F., Ungerechts, G., Wybranietz, W., Spiegel, M., Bernlohr, C., Cecconi, F., Gregor, M., Neubert, W. J., Schulze-Osthoff, K., Lauer, U. M. (2002). Caspase-8 and Apaf-1-independent Caspase-9 Activation in Sendai Virus-infected Cells. J. Biol. Chem. 277: 29817-29824 [Abstract] [Full Text]  
  • Cote, H. C.F., Brumme, Z. L., Craib, K. J.P., Alexander, C. S., Wynhoven, B., Ting, L., Wong, H., Harris, M., Harrigan, P. R., O'Shaughnessy, M. V., Montaner, J. S.G. (2002). Changes in Mitochondrial DNA as a Marker of Nucleoside Toxicity in HIV-Infected Patients. NEJM 346: 811-820 [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»