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 George, M. D.
Right arrow Articles by Dandekar, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by George, M. D.
Right arrow Articles by Dandekar, S.

 Previous Article  |  Next Article 

Journal of Virology, March 2005, p. 2709-2719, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2709-2719.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Early Antiretroviral Therapy for Simian Immunodeficiency Virus Infection Leads to Mucosal CD4+ T-Cell Restoration and Enhanced Gene Expression Regulating Mucosal Repair and Regeneration

Michael D. George, Elizabeth Reay, Sumathi Sankaran, and Satya Dandekar*

Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California

Received 10 September 2004/ Accepted 10 November 2004

Simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections lead to rapid depletion of CD4+ T cells from gut-associated lymphoid tissue (GALT). Although the administration of antiretroviral therapy (ART) has been shown to increase CD4+ T-cell levels in the peripheral blood in both SIV and HIV infections, its efficacy in restoring intestinal mucosal CD4+ T cells has not been well investigated. To gain insights into the molecular mechanisms of virally induced disruptions in the mucosal immune system, we have evaluated longitudinal changes in viral burden, T-cell subsets, and mucosal gene expression profiles in SIV-infected rhesus macaques in the absence or presence of ART. Our results demonstrate a dramatic suppression of mucosal viral loads and rapid reconstitution of CD4+ T cells in GALT in animals receiving ART that were not observed in untreated SIV-infected animals. DNA microarray-based gene expression profiling indicated that CD4+ T-cell restoration in GALT was associated with up regulation of growth factors and genes involved in repair and regeneration of the mucosal epithelium. In contrast, untreated SIV-infected animals increased expression of lymphocyte activation and inflammatory response-associated genes and did not up regulate mucosal growth and repair associated transcription. In conclusion, these data indicate that initiating ART in primary SIV infection may lead to the restoration of the mucosal immune system through reduction of inflammation and promotion of epithelial repair in the intestinal mucosa.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA 95616. Phone: (530) 752-3409. Fax: (530) 752-8692. E-mail: sdandekar{at}ucdavis.edu.

Journal of Virology, March 2005, p. 2709-2719, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2709-2719.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dinoso, J. B., Rabi, S. A., Blankson, J. N., Gama, L., Mankowski, J. L., Siliciano, R. F., Zink, M. C., Clements, J. E. (2009). A Simian Immunodeficiency Virus-Infected Macaque Model To Study Viral Reservoirs That Persist during Highly Active Antiretroviral Therapy. J. Virol. 83: 9247-9257 [Abstract] [Full Text]  
  • George, M. D., Verhoeven, D., Sankaran, S., Glavan, T., Reay, E., Dandekar, S. (2009). Heightened Cytotoxic Responses and Impaired Biogenesis Contribute to Early Pathogenesis in the Oral Mucosa of Simian Immunodeficiency Virus-Infected Rhesus Macaques. CVI 16: 277-281 [Abstract] [Full Text]  
  • Wright, A., Lamm, M. E., Huang, Y. T. (2008). Excretion of Human Immunodeficiency Virus Type 1 through Polarized Epithelium by Immunoglobulin A. J. Virol. 82: 11526-11535 [Abstract] [Full Text]  
  • Mohan, M., Aye, P. P., Borda, J. T., Alvarez, X., Lackner, A. A. (2008). CCAAT/Enhancer Binding Protein {beta} Is a Major Mediator of Inflammation and Viral Replication in the Gastrointestinal Tract of Simian Immunodeficiency Virus-Infected Rhesus Macaques. Am. J. Pathol. 173: 106-118 [Abstract] [Full Text]  
  • Verhoeven, D., Sankaran, S., Silvey, M., Dandekar, S. (2008). Antiviral Therapy during Primary Simian Immunodeficiency Virus Infection Fails To Prevent Acute Loss of CD4+ T Cells in Gut Mucosa but Enhances Their Rapid Restoration through Central Memory T Cells. J. Virol. 82: 4016-4027 [Abstract] [Full Text]  
  • Sankaran, S., George, M. D., Reay, E., Guadalupe, M., Flamm, J., Prindiville, T., Dandekar, S. (2008). Rapid Onset of Intestinal Epithelial Barrier Dysfunction in Primary Human Immunodeficiency Virus Infection Is Driven by an Imbalance between Immune Response and Mucosal Repair and Regeneration. J. Virol. 82: 538-545 [Abstract] [Full Text]  
  • Wang, H.-C., Dann, S. M., Okhuysen, P. C., Lewis, D. E., Chappell, C. L., Adler, D. G., White, A. C. Jr. (2007). High Levels of CXCL10 Are Produced by Intestinal Epithelial Cells in AIDS Patients with Active Cryptosporidiosis but Not after Reconstitution of Immunity. Infect. Immun. 75: 481-487 [Abstract] [Full Text]  
  • Guadalupe, M., Sankaran, S., George, M. D., Reay, E., Verhoeven, D., Shacklett, B. L., Flamm, J., Wegelin, J., Prindiville, T., Dandekar, S. (2006). Viral Suppression and Immune Restoration in the Gastrointestinal Mucosa of Human Immunodeficiency Virus Type 1-Infected Patients Initiating Therapy during Primary or Chronic Infection.. J. Virol. 80: 8236-8247 [Abstract] [Full Text]  
  • Murray, S. M., Picker, L. J., Axthelm, M. K., Linial, M. L. (2006). Expanded Tissue Targets for Foamy Virus Replication with Simian Immunodeficiency Virus-Induced Immunosuppression. J. Virol. 80: 663-670 [Abstract] [Full Text]  
  • Sankaran, S., Guadalupe, M., Reay, E., George, M. D., Flamm, J., Prindiville, T., Dandekar, S. (2005). Gut mucosal T cell responses and gene expression correlate with protection against disease in long-term HIV-1-infected nonprogressors. Proc. Natl. Acad. Sci. USA 102: 9860-9865 [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»