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 Badou, A.
Right arrow Articles by Bahraoui, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Badou, A.
Right arrow Articles by Bahraoui, E.

 Previous Article  |  Next Article 

Journal of Virology, November 2000, p. 10551-10562, Vol. 74, No. 22
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Tat Protein of Human Immunodeficiency Virus Type 1 Induces Interleukin-10 in Human Peripheral Blood Monocytes: Implication of Protein Kinase C-Dependent Pathway

Abdallah Badou,1 Yamina Bennasser,1 Marc Moreau,2 Catherine Leclerc,2 Monsef Benkirane,3 and Elmostafa Bahraoui1,*

Laboratoire d'Immuno-Virologie EA30381 and CNRS, Unité Mixte de Recherche 5547,2 Université Paul Sabatier, 31062 Toulouse Cedex, and Institut de Génétique Humaine, UPR1142, 34 396 Monpellier,3 France

Received 19 June 2000/Accepted 4 August 2000

The clinical manifestations observed in human immunodeficiency virus type 1 (HIV-1)-infected patients are primarily due to the capacity of the virus and its components to inactivate the immune system. HIV-1 Tat protein could participate in this immune system disorder. This protein is secreted by infected cells of HIV-infected patients and is free in the plasma, where it can interact and be taken up by both infected and noninfected cells. In asymptomatic patients infected by HIV-1, production of interleukin-10 (IL-10), a highly immunosuppressive cytokine, is associated with disease progression to AIDS. In the present work, we tested the capacity of Tat to induce IL-10 production by peripheral blood monocytes of healthy donors. The results show that Tat causes the production of IL-10 in a dose- and stimulation time-dependent manner. Investigations of the mechanisms involved in signal transduction show that (i) the calcium pathway is not or only slightly involved in Tat-induced IL-10 production, (ii) the protein kinase C pathway plays an essential role, and (iii) monocyte stimulation by Tat results in the intranuclear translocation of transcription factor NF-kappa B and in the induction of phosphorylation of the mitogen-activated protein kinases ERK1 and ERK2; activation of these two potential substrates of protein kinase C is required for the production of IL-10. Finally, our results suggest that the effect of Tat is exerted at the membrane level and that the active domain is located within N-terminal residues 1 to 45. This production of IL-10 induced by Tat could participate in the progression of HIV infection to AIDS.

* Corresponding author. Mailing address: Laboratoire d'Immuno-Virologie, Université Paul Sabatier, 118, route de Narbonne, 31062 Toulouse Cedex, France. Phone: (33) 561 558 667. Fax: (33) 561 558 667. E-mail: bahraoui{at}cict.fr.

Journal of Virology, November 2000, p. 10551-10562, Vol. 74, No. 22
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Brockman, M. A., Kwon, D. S., Tighe, D. P., Pavlik, D. F., Rosato, P. C., Sela, J., Porichis, F., Le Gall, S., Waring, M. T., Moss, K., Jessen, H., Pereyra, F., Kavanagh, D. G., Walker, B. D., Kaufmann, D. E. (2009). IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells. Blood 114: 346-356 [Abstract] [Full Text]  
  • Cheng, S. M., Li, J. C. B., Lin, S. S., Lee, D. C. W., Liu, L., Chen, Z., Lau, A. S. Y. (2009). HIV-1 transactivator protein induction of suppressor of cytokine signaling-2 contributes to dysregulation of IFN{gamma} signaling. Blood 113: 5192-5201 [Abstract] [Full Text]  
  • Green, K. A., Okazaki, T., Honjo, T., Cook, W. J., Green, W. R. (2008). The Programmed Death-1 and Interleukin-10 Pathways Play a Down-Modulatory Role in LP-BM5 Retrovirus-Induced Murine Immunodeficiency Syndrome. J. Virol. 82: 2456-2469 [Abstract] [Full Text]  
  • Gupta, S., Boppana, R., Mishra, G. C., Saha, B., Mitra, D. (2008). HIV-1 Tat Suppresses gp120-Specific T Cell Response in IL-10-Dependent Manner. J. Immunol. 180: 79-88 [Abstract] [Full Text]  
  • Campbell, G. R., Watkins, J. D., Singh, K. K., Loret, E. P., Spector, S. A. (2007). Human Immunodeficiency Virus Type 1 Subtype C Tat Fails To Induce Intracellular Calcium Flux and Induces Reduced Tumor Necrosis Factor Production from Monocytes. J. Virol. 81: 5919-5928 [Abstract] [Full Text]  
  • Gee, K., Angel, J. B., Mishra, S., Blahoianu, M. A., Kumar, A. (2007). IL-10 Regulation by HIV-Tat in Primary Human Monocytic Cells: Involvement of Calmodulin/Calmodulin-Dependent Protein Kinase-Activated p38 MAPK and Sp-1 and CREB-1 Transcription Factors. J. Immunol. 178: 798-807 [Abstract] [Full Text]  
  • Gee, K., Angel, J. B., Ma, W., Mishra, S., Gajanayaka, N., Parato, K., Kumar, A. (2006). Intracellular HIV-Tat Expression Induces IL-10 Synthesis by the CREB-1 Transcription Factor through Ser133 Phosphorylation and Its Regulation by the ERK1/2 MAPK in Human Monocytic Cells. J. Biol. Chem. 281: 31647-31658 [Abstract] [Full Text]  
  • Darnell, G. A., Schroder, W. A., Gardner, J., Harrich, D., Yu, H., Medcalf, R. L., Warrilow, D., Antalis, T. M., Sonza, S., Suhrbier, A. (2006). SerpinB2 Is an Inducible Host Factor Involved in Enhancing HIV-1 Transcription and Replication. J. Biol. Chem. 281: 31348-31358 [Abstract] [Full Text]  
  • Lee, H. Y., Kim, M.-K., Park, K. S., Shin, E. H., Jo, S. H., Kim, S. D., Jo, E. J., Lee, Y.-N., Lee, C., Baek, S.-H., Bae, Y.-S. (2006). Serum Amyloid A Induces Contrary Immune Responses via Formyl Peptide Receptor-Like 1 in Human Monocytes. Mol. Pharmacol. 70: 241-248 [Abstract] [Full Text]  
  • Campbell, G. R., Watkins, J. D., Esquieu, D., Pasquier, E., Loret, E. P., Spector, S. A. (2005). The C Terminus of HIV-1 Tat Modulates the Extent of CD178-mediated Apoptosis of T Cells. J. Biol. Chem. 280: 38376-38382 [Abstract] [Full Text]  
  • Ji, J., Sahu, G. K., Braciale, V. L., Cloyd, M. W. (2005). HIV-1 induces IL-10 production in human monocytes via a CD4-independent pathway. Int Immunol 17: 729-736 [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]  
  • Rayne, F., Vendeville, A., Bonhoure, A., Beaumelle, B. (2004). The Ability of Chloroquine To Prevent Tat-Induced Cytokine Secretion by Monocytes Is Implicated in Its In Vivo Anti-Human Immunodeficiency Virus Type 1 Activity. J. Virol. 78: 12054-12057 [Abstract] [Full Text]  
  • Nakamichi, K., Inoue, S., Takasaki, T., Morimoto, K., Kurane, I. (2004). Rabies Virus Stimulates Nitric Oxide Production and CXC Chemokine Ligand 10 Expression in Macrophages through Activation of Extracellular Signal-Regulated Kinases 1 and 2. J. Virol. 78: 9376-9388 [Abstract] [Full Text]  
  • Carbonneil, C., Donkova-Petrini, V., Aouba, A., Weiss, L. (2004). Defective Dendritic Cell Function in HIV-Infected Patients Receiving Effective Highly Active Antiretroviral Therapy: Neutralization of IL-10 Production and Depletion of CD4+CD25+ T Cells Restore High Levels of HIV-Specific CD4+ T Cell Responses Induced by Dendritic Cells Generated in the Presence of IFN-{alpha}. J. Immunol. 172: 7832-7840 [Abstract] [Full Text]  
  • Yang, Y., Tikhonov, I., Ruckwardt, T. J., Djavani, M., Zapata, J. C., Pauza, C. D., Salvato, M. S. (2003). Monocytes Treated with Human Immunodeficiency Virus Tat Kill Uninfected CD4+ Cells by a Tumor Necrosis Factor-Related Apoptosis-Induced Ligand-Mediated Mechanism. J. Virol. 77: 6700-6708 [Abstract] [Full Text]  
  • Mahot, S., Sergeant, A., Drouet, E., Gruffat, H. (2003). A novel function for the Epstein-Barr virus transcription factor EB1/Zta: induction of transcription of the hIL-10 gene. J. Gen. Virol. 84: 965-974 [Abstract] [Full Text]  
  • Tikhonov, I., Ruckwardt, T. J., Hatfield, G. S., Pauza, C. D. (2003). Tat-Neutralizing Antibodies in Vaccinated Macaques. J. Virol. 77: 3157-3166 [Abstract] [Full Text]  
  • Cota-Gomez, A., Flores, N. C., Cruz, C., Casullo, A., Aw, T. Y., Ichikawa, H., Schaack, J., Scheinman, R., Flores, S. C. (2002). The Human Immunodeficiency Virus-1 Tat Protein Activates Human Umbilical Vein Endothelial Cell E-selectin Expression via an NF-kappa B-dependent Mechanism. J. Biol. Chem. 277: 14390-14399 [Abstract] [Full Text]  
  • BENNASSER, Y., BAHRAOUI, E. (2002). HIV-1 Tat protein induces interleukin-10 in human peripheral blood monocytes: involvement of protein kinase C-{beta}II and -{delta}. FASEB J. 16: 546-554 [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»