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 Warby, T. J.
Right arrow Articles by Jaworowski, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Warby, T. J.
Right arrow Articles by Jaworowski, A.

 Previous Article  |  Next Article 

Journal of Virology, December 2003, p. 12630-12638, Vol. 77, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.23.12630-12638.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Infection Inhibits Granulocyte-Macrophage Colony-Stimulating Factor-Induced Activation of STAT5A in Human Monocyte-Derived Macrophages

Tammra J. Warby,1,2 Suzanne M. Crowe,1 and Anthony Jaworowski1*

AIDS Pathogenesis Research Unit, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, 3004 Victoria,1 Department of Microbiology and Parasitology, University of Queensland, St. Lucia, 4067 Queensland, Australia2

Received 21 March 2003/ Accepted 29 August 2003

Human immunodeficiency virus type 1 (HIV-1) infects cells of the monocyte/macrophage lineage. While infection of macrophages by HIV-1 is generally not cytopathic, it does impair macrophage function. In this study, we examined the effect of HIV-1 infection on intracellular signaling in human monocyte-derived macrophages (MDM) stimulated with the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is an important growth factor for cells of both the macrophage and granulocyte lineages and enhances effector functions of these cells via the heterodimeric GM-CSF receptor (GM-CSFR). A major pathway which mediates the effects of GM-CSF on macrophages involves activation of the latent transcription factor STAT5A via a Janus kinase 2 (JAK2)-dependent pathway. We demonstrate that GM-CSF-induced activation of STAT5A is inhibited in MDM after infection in vitro with the laboratory-adapted R5 strain of HIV-1, HIV-1Ba-L, but not after infection with adenovirus. HIV-1 infection of MDM did not decrease the STAT5A or JAK2 mRNA level or STAT5A protein level or result in increased constitutive activation of STAT5A. Surface expression of either the {alpha}-chain or common ßc-chain of GM-CSFR was also unaffected. We conclude that HIV-1 inhibits GM-CSF activation of STAT5A without affecting expression of the known components of the signaling pathway. These data provide further evidence of disruption of cellular signaling pathways after HIV-1 infection, which may contribute to immune dysfunction and HIV-1 pathogenesis.

* Corresponding author. Mailing address: AIDS Pathogenesis Research Unit, Macfarlane Burnet Institute for Medical Research and Public Health, GPO Box 2284, Melbourne, 3001 Victoria, Australia. Phone: 61 (03) 9282 2127. Fax: 61 (03) 9282 2142. E-mail: anthonyj{at}burnet.edu.au.

Journal of Virology, December 2003, p. 12630-12638, Vol. 77, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.23.12630-12638.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Joshi, P. C., Raynor, R., Fan, X., Guidot, D. M. (2008). HIV-1-Transgene Expression in Rats Decreases Alveolar Macrophage Zinc Levels and Phagocytosis. Am. J. Respir. Cell Mol. Bio. 39: 218-226 [Abstract] [Full Text]  
  • Lee, A. W., Sharp, E. R., O'Mahony, A., Rosenberg, M. G., Israelski, D. M., Nolan, G. P., Nixon, D. F. (2008). Single-Cell, Phosphoepitope-Specific Analysis Demonstrates Cell Type- and Pathway-Specific Dysregulation of Jak/STAT and MAPK Signaling Associated with In Vivo Human Immunodeficiency Virus Type 1 Infection. J. Virol. 82: 3702-3712 [Abstract] [Full Text]  
  • Tanimoto, A., Murata, Y., Wang, K.-Y., Tsutsui, M., Kohno, K., Sasaguri, Y. (2008). Monocyte Chemoattractant Protein-1 Expression Is Enhanced by Granulocyte-Macrophage Colony-stimulating Factor via Jak2-Stat5 Signaling and Inhibited by Atorvastatin in Human Monocytic U937 Cells. J. Biol. Chem. 283: 4643-4651 [Abstract] [Full Text]  
  • Queen, M. M., Ryan, R. E., Holzer, R. G., Keller-Peck, C. R., Jorcyk, C. L. (2005). Breast Cancer Cells Stimulate Neutrophils to Produce Oncostatin M: Potential Implications for Tumor Progression. Cancer Res. 65: 8896-8904 [Abstract] [Full Text]  
  • Suh, H.-S., Kim, M.-O., Lee, S. C. (2005). Inhibition of Granulocyte-Macrophage Colony-Stimulating Factor Signaling and Microglial Proliferation by Anti-CD45RO: Role of Hck Tyrosine Kinase and Phosphatidylinositol 3-Kinase/Akt. J. Immunol. 174: 2712-2719 [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»