HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0803222v1 183/3/1975    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Li, Q. Articles by Haase, A. T. PubMed PubMed Citation Articles by Li, Q. Articles by Haase, A. T. Pubmed/NCBI databases GEO DataSet

Microarray Analysis of Lymphatic Tissue Reveals Stage-Specific, Gene Expression Signatures in HIV-1 Infection¹

Qingsheng Li^2,*, Anthony J. Smith^2,*, Timothy W. Schacker, John V. Carlis, Lijie Duan^*, Cavan S. Reilly and Ashley T. Haase^3,*

*Department of Microbiology Division of Infectious Diseases, Department of Medicine, Medical School Department of Computer Science and Engineering, Institute of Technology, and Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455

Untreated HIV-1 infection progresses through acute and asymptomatic stages to AIDS. Although each of the three stages has well-known clinical, virologic, and immunologic characteristics, much less is known of the molecular mechanisms underlying each stage. In this study, we report lymphatic tissue microarray analyses, revealing for the first time stage-specific patterns of gene expression during HIV-1 infection. We show that although there is a common set of key genes with altered expression throughout all stages, each stage has a unique gene expression signature. The acute stage is most notably characterized by increased expression of hundreds of genes involved in immune activation, innate immune defenses (e.g., RIG-1, MDA-5, TLR7 and TLR8, PKR, APOBEC3B, 3F, 3G), adaptive immunity, and in the proapoptotic Fas-Fas ligand pathway. Yet, quite strikingly, the expression of nearly all acute stage genes return to baseline levels in the asymptomatic stage, accompanying partial control of infection. This transition from acute to asymptomatic stage is tied to increased expression of a diverse array of immunosuppressive genes (e.g., CLEC12B, ILT4, galectin-3, CD160, BCMA, FGL2, LAG3, GPNMB). In the AIDS stage, decreased expression of numerous genes involved in T cell signaling identifies genes contributing to T cell dysfunction. These common and stage-specific gene expression signatures identify potential molecular mechanisms underlying the host response and the slow, natural course of HIV-1 infection.

³ Address correspondence and reprint requests to Dr. Ashley T. Haase, Department of Microbiology, University of Minnesota, MMC 196, 420 Delaware Street Southeast, Minneapolis, MN 55455. E-mail address: haase001{at}umn.edu

¹ This work was supported by Public Health Services Grant R01 AI056997 from the National Institute of Allergy and Infectious Diseases.

² Q.L. and A.J.S. contributed equally to this work.