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

 Previous Article  |  Next Article 

Journal of Virology, August 2006, p. 8236-8247, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00120-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Viral Suppression and Immune Restoration in the Gastrointestinal Mucosa of Human Immunodeficiency Virus Type 1-Infected Patients Initiating Therapy during Primary or Chronic Infection

Moraima Guadalupe,1 Sumathi Sankaran,1 Michael D. George,1 Elizabeth Reay,1 David Verhoeven,1 Barbara L. Shacklett,1 Jason Flamm,4 Jacob Wegelin,3 Thomas Prindiville,2 and Satya Dandekar1*

Department of Medical Microbiology and Immunology,1 Department of Internal Medicine,2 Department of Public Health Sciences, School of Medicine, University of California, Davis, California,3 Kaiser Permanente Medical Group, Sacramento, California4

Received 17 January 2006/ Accepted 16 May 2006

Although the gut-associated lymphoid tissue (GALT) is an important early site for human immunodeficiency virus (HIV) replication and severe CD4+ T-cell depletion, our understanding is limited about the restoration of the gut mucosal immune system during highly active antiretroviral therapy (HAART). We evaluated the kinetics of viral suppression, CD4+ T-cell restoration, gene expression, and HIV-specific CD8+ T-cell responses in longitudinal gastrointestinal biopsy and peripheral blood samples from patients initiating HAART during primary HIV infection (PHI) or chronic HIV infection (CHI) using flow cytometry, real-time PCR, and DNA microarray analysis. Viral suppression was more effective in GALT of PHI patients than CHI patients during HAART. Mucosal CD4+ T-cell restoration was delayed compared to peripheral blood and independent of the time of HAART initiation. Immunophenotypic analysis showed that repopulating mucosal CD4+ T cells were predominantly of a memory phenotype and expressed CD11{alpha}, {alpha}Eß7, CCR5, and CXCR4. Incomplete suppression of viral replication in GALT during HAART correlated with increased HIV-specific CD8+ T-cell responses. DNA microarray analysis revealed that genes involved in inflammation and cell activation were up regulated in patients who did not replenish mucosal CD4+ T cells efficiently, while expression of genes involved in growth and repair was increased in patients with efficient mucosal CD4+ T-cell restoration. Our findings suggest that the discordance in CD4+ T-cell restoration between GALT and peripheral blood during therapy can be attributed to the incomplete viral suppression and increased immune activation and inflammation that may prevent restoration of CD4+ T cells and the gut microenvironment.

* Corresponding author. Mailing address: Dept. of Medical Microbiology and Immunology, GBSF, Room 5511, University of California, Davis, CA 95616. Phone: (530) 752-3409. Fax: (530) 752-7301. E-mail: sdandekar{at}ucdavis.edu.

Journal of Virology, August 2006, p. 8236-8247, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00120-06
Copyright © 2006, 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]  
  • Shen, R., Richter, H. E., Clements, R. H., Novak, L., Huff, K., Bimczok, D., Sankaran-Walters, S., Dandekar, S., Clapham, P. R., Smythies, L. E., Smith, P. D. (2009). Macrophages in Vaginal but Not Intestinal Mucosa Are Monocyte-Like and Permissive to Human Immunodeficiency Virus Type 1 Infection. J. Virol. 83: 3258-3267 [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]  
  • Gordon, S. N., Klatt, N. R., Bosinger, S. E., Brenchley, J. M., Milush, J. M., Engram, J. C., Dunham, R. M., Paiardini, M., Klucking, S., Danesh, A., Strobert, E. A., Apetrei, C., Pandrea, I. V., Kelvin, D., Douek, D. C., Staprans, S. I., Sodora, D. L., Silvestri, G. (2007). Severe Depletion of Mucosal CD4+ T Cells in AIDS-Free Simian Immunodeficiency Virus-Infected Sooty Mangabeys. J. Immunol. 179: 3026-3034 [Abstract] [Full Text]  
  • Sundstrom, J. B., Ellis, J. E., Hair, G. A., Kirshenbaum, A. S., Metcalfe, D. D., Yi, H., Cardona, A. C., Lindsay, M. K., Ansari, A. A. (2007). Human tissue mast cells are an inducible reservoir of persistent HIV infection. Blood 109: 5293-5300 [Abstract] [Full Text]  
  • Critchfield, J. W., Lemongello, D., Walker, D. H., Garcia, J. C., Asmuth, D. M., Pollard, R. B., Shacklett, B. L. (2007). Multifunctional Human Immunodeficiency Virus (HIV) Gag-Specific CD8+ T-Cell Responses in Rectal Mucosa and Peripheral Blood Mononuclear Cells during Chronic HIV Type 1 Infection. J. Virol. 81: 5460-5471 [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»