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

 Previous Article  |  Next Article 

Journal of Virology, January 2008, p. 538-545, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01449-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Sumathi Sankaran,1 Michael D. George,1 Elizabeth Reay,1 Moraima Guadalupe,1 Jason Flamm,3 Thomas Prindiville,2 and Satya Dandekar1*

Department of Medical Microbiology and Immunology, University of California, Davis, California 95616,1 Division of Gastroenterology, University of California, Davis, California,2 The Permanente Medical Group, Inc., Sacramento, California, 961853

Received 3 July 2007/ Accepted 11 October 2007

Gut-associated lymphoid tissue (GALT) is an early target for human immunodeficiency virus type 1 (HIV-1) infection and is a site for severe CD4+ T-cell depletion. HIV-associated enteropathy is well-documented in chronic HIV-1 infection. However, the initial host responses to HIV infection in GALT and the early molecular correlates of HIV enteropathogenesis have not been characterized during primary HIV infection. In this study, we provide evidence of viral replication in GALT resident CD4+ T cells and macrophages in primary-stage patients and identify early patterns of host mucosal responses and changes in the molecular microenvironment through gene expression profiling. High levels of viral replication in GALT and marked CD4+ T-cell depletion correlated with decreased expression levels of genes regulating epithelial barrier maintenance and digestive/metabolic functions. These changes coincided with a marked increase in the transcription of immune activation-, inflammation-, and apoptosis-associated genes. Our findings indicate that HIV-induced pathogenesis in GALT emerges at both the molecular and cellular levels prior to seroconversion in primary HIV infection, potentially setting the stage for disease progression by impairing the ability to control viral replication and repair and regenerate intestinal mucosal tissues.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology, University of California, Davis, Tupper Hall, Room 3146, Davis, CA 95616. Phone: (530) 752-3409. Fax: (530) 754-7240. E-mail: sdandekar{at}ucdavis.edu

{triangledown} Published ahead of print on 24 October 2007.

Journal of Virology, January 2008, p. 538-545, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01449-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Fontenot, D., He, H., Hanabuchi, S., Nehete, P. N., Zhang, M., Chang, M., Nehete, B., Wang, Y.-H., Wang, Y.-H., Ma, Z.-m., Lee, H.-C., Ziegler, S. F., Courtney, A. N., Miller, C. J., Sun, S.-C., Liu, Y.-J., Sastry, K. J. (2009). TSLP production by epithelial cells exposed to immunodeficiency virus triggers DC-mediated mucosal infection of CD4+ T cells. Proc. Natl. Acad. Sci. USA 106: 16776-16781 [Abstract] [Full Text]  
  • Westhorpe, C. L. V., Zhou, J., Webster, N. L., Kalionis, B., Lewin, S. R., Jaworowski, A., Muller, W. A., Crowe, S. M. (2009). Effects of HIV-1 infection in vitro on transendothelial migration by monocytes and monocyte-derived macrophages. J. Leukoc. Biol. 85: 1027-1035 [Abstract] [Full Text]  
  • Alfano, M., Mariani, S. A., Elia, C., Pardi, R., Blasi, F., Poli, G. (2009). Ligand-engaged urokinase-type plasminogen activator receptor and activation of the CD11b/CD18 integrin inhibit late events of HIV expression in monocytic cells. Blood 113: 1699-1709 [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]  
  • Gumbi, P. P., Nkwanyana, N. N., Bere, A., Burgers, W. A., Gray, C. M., Williamson, A.-L., Hoffman, M., Coetzee, D., Denny, L., Passmore, J.-A. S. (2008). Impact of Mucosal Inflammation on Cervical Human Immunodeficiency Virus (HIV-1)-Specific CD8 T-Cell Responses in the Female Genital Tract during Chronic HIV Infection. J. Virol. 82: 8529-8536 [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»