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 Schmitt, N.
Right arrow Articles by Israël, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schmitt, N.
Right arrow Articles by Israël, N.

 Previous Article  |  Next Article 

Journal of Virology, May 2003, p. 5784-5793, Vol. 77, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.10.5784-5793.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Positive Regulation of CXCR4 Expression and Signaling by Interleukin-7 in CD4+ Mature Thymocytes Correlates with Their Capacity To Favor Human Immunodeficiency X4 Virus Replication

Nathalie Schmitt, Laurent Chêne, David Boutolleau, Marie-Thérèse Nugeyre, Eric Guillemard, Pierre Versmisse, Catherine Jacquemot, Françoise Barré-Sinoussi, and Nicole Israël*

Unité de Biologie des Rétrovirus, Institut Pasteur, 75724 Paris Cedex 15, France

Received 16 December 2002/ Accepted 27 February 2003

The emergence of X4 human immunodeficiency virus type 1 (HIV-1) variants in infected individuals is associated with poor prognosis. One of the possible causes of this emergence might be the selection of X4 variants in some specific tissue compartment. We demonstrate that the thymic microenvironment favors the replication of X4 variants by positively modulating the expression and signaling of CXCR4 in mature CD4+ CD8- CD3+ thymocytes. Here, we show that the interaction of thymic epithelial cells (TEC) with these thymocytes in culture induces an upregulation of CXCR4 expression. The cytokine secreted by TEC, interleukin-7 (IL-7), increases cell surface expression of CXCR4 and efficiently overcomes the downregulation induced by SDF-1{alpha}, also produced by TEC. IL-7 also potentiates CXCR4 signaling, leading to actin polymerization, a process necessary for virus entry. In contrast, in intermediate CD4+ CD8- CD3- thymocytes, the other subpopulation known to allow virus replication, TEC or IL-7 has little or no effect on CXCR4 expression and signaling. CCR5 is expressed at similarly low levels in the two thymocyte subpopulations, and neither its expression nor its signaling was modified by the cytokines tested. This positive regulation of CXCR4 by IL-7 in mature CD4+ thymocytes correlates with their high capacity to favor X4 virus replication compared with intermediate thymocytes or peripheral blood mononuclear cells. Indeed, we observed an enrichment of X4 viruses after replication in thymocytes initially infected with a mixture of X4 (NL4-3) and R5 (NLAD8) HIV strains and after the emergence of X4 variants from an R5 primary isolate during culture in mature thymocytes.

* Corresponding author. Mailing address: Unité de Biologie des Rétrovirus, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: 33 1 4568 8944. Fax: 33 1 4568 8957. E-mail: nisrael{at}pasteur.fr.

Journal of Virology, May 2003, p. 5784-5793, Vol. 77, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.10.5784-5793.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Donaghy, H., Wilkinson, J., Cunningham, A. L. (2006). HIV interactions with dendritic cells: has our focus been too narrow?. J. Leukoc. Biol. 80: 1001-1012 [Abstract] [Full Text]  
  • Zaunders, J. J., Ip, S., Munier, M. L., Kaufmann, D. E., Suzuki, K., Brereton, C., Sasson, S. C., Seddiki, N., Koelsch, K., Landay, A., Grey, P., Finlayson, R., Kaldor, J., Rosenberg, E. S., Walker, B. D., Fazekas de St. Groth, B., Cooper, D. A., Kelleher, A. D., on Behalf of the PHAEDRA Study Team, (2006). Infection of CD127+ (Interleukin-7 Receptor+) CD4+ Cells and Overexpression of CTLA-4 Are Linked to Loss of Antigen-Specific CD4 T Cells during Primary Human Immunodeficiency Virus Type 1 Infection.. J. Virol. 80: 10162-10172 [Abstract] [Full Text]  
  • Delobel, P., Nugeyre, M.-T., Cazabat, M., Sandres-Saune, K., Pasquier, C., Cuzin, L., Marchou, B., Massip, P., Cheynier, R., Barre-Sinoussi, F., Izopet, J., Israel, N. (2006). Naive T-cell depletion related to infection by x4 human immunodeficiency virus type 1 in poor immunological responders to highly active antiretroviral therapy.. J. Virol. 80: 10229-10236 [Abstract] [Full Text]  
  • Beq, S., Nugeyre, M.-T., Fang, R. H. T., Gautier, D., Legrand, R., Schmitt, N., Estaquier, J., Barre-Sinoussi, F., Hurtrel, B., Cheynier, R., Israel, N. (2006). IL-7 Induces Immunological Improvement in SIV-Infected Rhesus Macaques under Antiviral Therapy. J. Immunol. 176: 914-922 [Abstract] [Full Text]  
  • Audige, A., Schlaepfer, E., Joller, H., Speck, R. F. (2005). Uncoupled Anti-HIV and Immune-Enhancing Effects when Combining IFN-{alpha} and IL-7. J. Immunol. 175: 3724-3736 [Abstract] [Full Text]  
  • Choudhary, S. K., Choudhary, N. R., Kimbrell, K. C., Colasanti, J., Ziogas, A., Kwa, D., Schuitemaker, H., Camerini, D. (2005). R5 Human Immunodeficiency Virus Type 1 Infection of Fetal Thymic Organ Culture Induces Cytokine and CCR5 Expression. J. Virol. 79: 458-471 [Abstract] [Full Text]  
  • Nugeyre, M.-T., Monceaux, V., Beq, S., Cumont, M.-C., Fang, R. H. T., Chene, L., Morre, M., Barre-Sinoussi, F., Hurtrel, B., Israel, N. (2003). IL-7 Stimulates T Cell Renewal Without Increasing Viral Replication in Simian Immunodeficiency Virus-Infected Macaques. J. Immunol. 171: 4447-4453 [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»