title: Constitutive expression of IRF-5 in HTLV-1-infected T cells.
abstract: Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), an aggressive and fatal leukemia of T cells. Interferon regulatory factor (IRF)-5 plays a critical role in the induction of interferon genes in viral infected cells. We examined the specific mechanisms underlying the expression and regulation of IRF-5 in HTLV-1-infected T cells. IRF-5 was constitutively transcribed into three distinct alternatively spliced isoforms (V1, V3 and V4) in HTLV-1-infected T-cell lines but not in uninfected T-cell lines. IRF-5 was also upregulated in HTLV-1-infected T-cell lines at protein level. Nuclear IRF-5 expression was noted in ATL cells present in lymph nodes and skin lesions. IRF-5 mRNA expression was induced following infection of T cells with HTLV-1, and specifically by viral oncoprotein Tax. Tax also activated V3 promoter. Microarray analysis of IRF-5-expressing uninfected T cells demonstrated that IRF-5 induced the expression of tumor necrosis factor family cytokines. The results suggest that IRF-5 is a Tax-regulated gene, and its expression may be associated with the pathogenesis of ATL.
authors.affiliation: Transdisciplinary Research Organization for Subtropics and Island Studies, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Ishikawa
authors.affiliation: Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.
authors.forename: Masachika
authors.initials: M
authors.lastname: Senba
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers Biomedical and Health Sciences, Newark, NJ 07103, USA.
authors.forename: Betsy J
authors.initials: BJ
authors.lastname: Barnes
authors.affiliation: Department of Microbiology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
mesh_terms: D017398:Alternative Splicing; D002460:Cell Line; D002461:Cell Line, Transformed; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism*; D019169:Jurkat Cells; D020033:Protein Isoforms / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D048069:Tumor Necrosis Factors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016356:Gene Products, tax; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D020033:Protein Isoforms; D048069:Tumor Necrosis Factors