NFAT1 enhances HIV-1 gene expression in primary human CD4 T cells.
In: Clinical immunology (Orlando, Fla.), Jg. 94 (2000-03-01), Heft 3, S. 179-91
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Zugriff:
Cyclosporin A (CsA) is a potent inhibitor of the NFAT family of transcription factors that enhance T cell activation. The observation that human immunodeficiency virus type 1 (HIV-1)-positive transplant recipients have a reduced HIV-1 viral burden during treatment with CsA suggested that NFAT may play a direct role in enhancing transcription of the HIV-1 viral genome. Two sets of NFAT binding sites were identified in the HIV-1 long terminal repeat (LTR) promoter by in vitro footprinting with full-length recombinant NFAT protein, and gel shift analysis of nuclear protein from polyclonally activated primary CD4 T cells revealed specific binding of NFAT1 to the NFkappaB binding sites of the HIV-1 LTR. Activation of primary CD4 T cells transiently transfected with a HIV-1 LTR luciferase reporter plasmid, lacking the NFAT binding sites in the upstream putative negative regulatory element but maintaining the NFkappaB/NFAT sites, demonstrated increased HIV-1 gene expression when cotransfected with a NFAT1 expression vector. Moreover, CsA, FK506, and a dominant-negative NFAT1 protein independently inhibited HIV-1 LTR promoter activity in CD4 T cells stimulated with phorbol ester and calcium ionophore. In primary human CD4 T cells, CsA also inhibited promoter activity directed by multimers of binding sites for NFAT, while having no effect on NFkappaB multimer-driven promoter activity. Increasing NFAT1 levels in CD4 T cells transiently transfected with a HIV-1 provirus also increased p24 protein expression. Thus, NFAT may be a target for prevention of HIV-1 LTR-directed gene expression in human CD4 T cells.
(Copyright 2000 Academic Press.)
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NFAT1 enhances HIV-1 gene expression in primary human CD4 T cells.
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Autor/in / Beteiligte Person: | Cron, RQ ; Bartz, SR ; Clausell, A ; Bort, SJ ; Klebanoff, SJ ; Lewis, DB |
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Zeitschrift: | Clinical immunology (Orlando, Fla.), Jg. 94 (2000-03-01), Heft 3, S. 179-91 |
Veröffentlichung: | Orlando, FL : Academic Press, c1999-, 2000 |
Medientyp: | academicJournal |
ISSN: | 1521-6616 (print) |
DOI: | 10.1006/clim.1999.4831 |
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