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

J. Biol. Chem., Vol. 282, Issue 22, 15973-15980, June 1, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/22/15973    most recent M702051200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holmes, D. Articles by Su, L. Search for Related Content PubMed PubMed Citation Articles by Holmes, D. Articles by Su, L. Social Bookmarking                      What's this?

FoxP3 Enhances HIV-1 Gene Expression by Modulating NFB Occupancy at the Long Terminal Repeat in Human T Cells^*

Derek Holmes, Geoffry Knudsen, Stephanie Mackey-Cushman, and Lishan Su^¶1

From the Department of Microbiology and Immunology, the Lineberger Comprehensive Cancer Center, and the ^¶Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7295

FoxP3 determines the development of CD4+CD25+ regulatory T (Treg) cells and represses interleukin-2 (IL-2) expression in Treg cells. However, human immunodeficiency virus type 1 (HIV-1) infects and replicates efficiently in FoxP3+ Treg cells. We report that, while inhibiting IL-2 gene expression, FoxP3 enhances gene expression from HIV-1 long terminal repeat (LTR). This FoxP3 activity requires both the N- and C-terminal domains and is inactivated by human IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome) mutations. FoxP3 enhances HIV-1 LTR via its specific NFB binding sequences in an NFB-dependent fashion in T cells but not in HEK293 cells. FoxP3 decreases level of histone acetylation at the interleukin-2 locus but not at the HIV-1 LTR. Although NFB nuclear translocation is not altered, FoxP3 enhances NFB-p65 binding to HIV-1 LTR. These data suggest that FoxP3 modulates gene expression in a promoter sequence-dependent fashion by modulating chromatin structure and NFB activity. HIV-1 LTR has evolved to both highjack the T-cell activation pathway for expression and to resist FoxP3-mediated suppression of T-cell activation.

Received for publication, March 8, 2007 , and in revised form, March 28, 2007.

^* The project was supported by National Institutes of Health Grants AI048407 (to L. S.) and 5T32AI07273 (to G. K.). The authors declare no competing financial interests. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

¹ To whom correspondence should be addressed: Dept. of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7295. Tel.: 919-966-6654; Fax: 919-966-8212; E-mail: lsu{at}med.unc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. Dean Acute HIV-1 infection: targeting the regulator Blood, October 1, 2008; 112(7): 2600 - 2600. [Full Text] [PDF]

				Q. Jiang, L. Zhang, R. Wang, J. Jeffrey, M. L. Washburn, D. Brouwer, S. Barbour, G. I. Kovalev, D. Unutmaz, and L. Su FoxP3+CD4+ regulatory T cells play an important role in acute HIV-1 infection in humanized Rag2-/-{gamma}C-/- mice in vivo Blood, October 1, 2008; 112(7): 2858 - 2868. [Abstract] [Full Text] [PDF]

				A. J. Chase, H.-C. Yang, H. Zhang, J. N. Blankson, and R. F. Siliciano Preservation of FoxP3+ Regulatory T Cells in the Peripheral Blood of Human Immunodeficiency Virus Type 1-Infected Elite Suppressors Correlates with Low CD4+ T-Cell Activation J. Virol., September 1, 2008; 82(17): 8307 - 8315. [Abstract] [Full Text] [PDF]

				M. F. Nold, C. A. Nold-Petry, G. B. Pott, J. A. Zepp, M. T. Saavedra, S.-H. Kim, and C. A. Dinarello Endogenous IL-32 Controls Cytokine and HIV-1 Production J. Immunol., July 1, 2008; 181(1): 557 - 565. [Abstract] [Full Text] [PDF]

				A. K. Antons, R. Wang, K. Oswald-Richter, M. Tseng, C. W. Arendt, S. A. Kalams, and D. Unutmaz Naive Precursors of Human Regulatory T Cells Require FoxP3 for Suppression and Are Susceptible to HIV Infection J. Immunol., January 15, 2008; 180(2): 764 - 773. [Abstract] [Full Text] [PDF]

				A. J. Chase, A. R. Sedaghat, J. R. German, L. Gama, M. C. Zink, J. E. Clements, and R. F. Siliciano Severe Depletion of CD4+ CD25+ Regulatory T Cells from the Intestinal Lamina Propria but Not Peripheral Blood or Lymph Nodes during Acute Simian Immunodeficiency Virus Infection J. Virol., December 1, 2007; 81(23): 12748 - 12757. [Abstract] [Full Text] [PDF]