期刊
VIROLOGY
卷 381, 期 2, 页码 161-167出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2008.08.033
关键词
T-cells; Human; Transcription factors; Gene regulation; HIV-1; FOXP3; NFAT2; ETR
类别
资金
- National Institutes of Health (NIH) [P30 A145008, R01 A135513]
- Joseph L. Hollander Chair
- Mary L. Smith Charitable Trust
- Elizabeth Glaser Pediatric AIDS Foundation
- Joseph Stokes Jr. Research Institute
- Penn Cancer Center
- NIH AIDS Research and Reference Reagent Program
- University of Pennsylvania Center for AIDS Research
FOXP3 is a necessary transcription factor for the development and function of CD4+ regulatory T-cells (Tregs). The role of Tregs in HIV-1 infection remains unclear. Here, we show that expression of FOXP3 in primary human CD4 T-cells significantly inhibits HIV-1 infection. Since FOXP3 inhibits NFAT activity, and NFAT proteins contribute to HIV-1 transcription, we explore a transcriptional repressive function of HIV-1 LTR by FOXP3. Over-expression of FOXP3 in primary CD4 T-cells inhibits wild-type HIV-1 LTR reporter activity, and truncation mutants demonstrate that repression of the LTR by FOXP3 requires the dual proximal NF kappa B/NFAT binding sites. interestingly, FOXP3 decreases binding of NFAT2 to the HIV-1 LTR in vivo. Furthermore, FOXP3 does not inhibit infection of HIV-1 NL4-3 which is mutated to disrupt transcription factor binding at either proximal NFAT or NF kappa B binding sites. These data suggest that resistance of Tregs; to HIV-1 infection is due to inhibition of HIV-1 LTR transcription by FOXP3. (C) 2008 Elsevier Inc. All rights reserved.
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