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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.<\/jats:p>","DOI":"10.1189\/jlb.1205723","type":"journal-article","created":{"date-parts":[[2006,7,8]],"date-time":"2006-07-08T00:44:38Z","timestamp":1152319478000},"page":"640-650","source":"Crossref","is-referenced-by-count":16,"title":["AP-1-directed human T cell leukemia virus type 1 viral gene expression during monocytic differentiation"],"prefix":"10.1093","volume":"80","author":[{"given":"Christian","family":"Grant","sequence":"first","affiliation":[{"name":"Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland"},{"name":"Department of Micrbiology and Immunology, and Center for Molecular Virology and Neuroimmunology, Center for Cancer Biology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Micrbiology and Immunology, and Center for Molecular Virology and Neuroimmunology, Center for Cancer Biology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Nonnemacher","sequence":"additional","affiliation":[{"name":"Department of Micrbiology and Immunology, and Center for Molecular Virology and Neuroimmunology, Center for Cancer Biology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E","family":"Flaig","sequence":"additional","affiliation":[{"name":"Department of Micrbiology and Immunology, and Center for Molecular Virology and Neuroimmunology, Center for Cancer Biology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Irish","sequence":"additional","affiliation":[{"name":"Department of Micrbiology and Immunology, and Center for Molecular Virology and Neuroimmunology, Center for Cancer Biology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya","family":"Ahuja","sequence":"additional","affiliation":[{"name":"Department of Micrbiology and Immunology, and Center for Molecular Virology and Neuroimmunology, Center for Cancer Biology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Alexaki","sequence":"additional","affiliation":[{"name":"Department of Micrbiology and Immunology, and Center for Molecular Virology and Neuroimmunology, Center for Cancer Biology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Alefantis","sequence":"additional","affiliation":[{"name":"Vital Probes, Inc. , Mayfield, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Wigdahl","sequence":"additional","affiliation":[{"name":"Department of Micrbiology and Immunology, and Center for Molecular Virology and Neuroimmunology, Center for Cancer Biology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine , Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,7,7]]},"reference":[{"key":"2023033007512290100_jlb0640-cit-B1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1742-4690-2-17","article-title":"The discovery of the first human retrovirus: HTLV-1 and HTLV-2","volume":"2","author":"Gallo","year":"2005","journal-title":"Retrovirology"},{"key":"2023033007512290100_jlb0640-cit-B2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/S0140-6736(85)92734-5","article-title":"Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis","volume":"2","author":"Gessain","year":"1985","journal-title":"Lancet"},{"key":"2023033007512290100_jlb0640-cit-B3","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S0140-6736(86)91298-5","article-title":"HTLV-I associated myelopathy, a new clinical 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