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AP-1-directed human T cell leukemia virus type 1 viral gene expression during monocytic differentiation
Journal article   Peer reviewed

AP-1-directed human T cell leukemia virus type 1 viral gene expression during monocytic differentiation

Christian Grant, Pooja Jain, Michael Nonnemacher, Katherine E Flaig, Bryan Irish, Jaya Ahuja, Aikaterini Alexaki, Timothy Alefantis and Brian Wigdahl
Journal of leukocyte biology, v 80(3), pp 640-650
Sep 2006
DOI: https://doi.org/10.1189/jlb.1205723
PMID: 16829632
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Gene Products, tax - immunology Human T-lymphotropic virus 1 - isolation & purification Tetradecanoylphorbol Acetate - pharmacology Humans Molecular Sequence Data Tetradecanoylphorbol Acetate - analogs & derivatives Gene Expression Regulation, Viral - genetics Monocytes - immunology Monocytes - drug effects Cell Differentiation - immunology Monocytes - virology Up-Regulation - immunology Cell Differentiation - drug effects Base Sequence Transcription Factor AP-1 - physiology Protein Binding Human T-lymphotropic virus 1 - genetics Human T-lymphotropic virus 1 - immunology Genes, fos - immunology
Human T cell leukemia virus type 1 (HTLV-1) has previously been shown to infect antigen-presenting cells and their precursors in vivo. However, the role these important cell populations play in the pathogenesis of HTLV-1-associated myelopathy/tropical spastic paraparesis or adult T cell leukemia remains unresolved. To better understand how HTLV-1 infection of these important cell populations may potentially impact disease progression, the regulation of HTLV-1 viral gene expression in established monocytic cell lines was examined. U-937 promonocytic cells transiently transfected with a HTLV-1 long-terminal repeat (LTR) luciferase construct were treated with phorbol 12-myristate 13-acetate (PMA) to induce cellular differentiation. PMA-induced cellular differentiation resulted in activation of basal and Tax-mediated transactivation of the HTLV-1 LTR. In addition, electrophoretic mobility shift analyses demonstrated that PMA-induced cellular differentiation induced DNA-binding activity of cellular transcription factors to Tax-responsive element 1 (TRE-1) repeat II. Supershift analyses revealed that factors belonging to the activator protein 1 (AP-1) family of basic region/leucine zipper proteins (Fra-1, Fra-2, JunB, and JunD) were induced to bind to TRE-1 repeat II during cellular differentiation. Inhibition of AP-1 DNA-binding activity by overexpression of a dominant-negative c-Fos mutant (A-Fos) in transient expression analyses resulted in severely decreased levels of HTLV-1 LTR activation in PMA-induced U-937 cells. These results have suggested that following infection of peripheral blood monocytes, HTLV-1 viral gene expression may become up-regulated by AP-1 during differentiation into macrophages or dendritic cells.

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Web of Science research areas
Cell Biology
Hematology
Immunology
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