title: Human T-cell leukemia virus type 1 (HTLV-1) Tax1 oncoprotein but not HTLV-2 Tax2 induces the expression of OX40 ligand by interacting with p52/p100 and RelB.
abstract: Human T-cell leukemia virus type 1 (HTLV-1) is a causative retrovirus of adult T-cell leukemia and HTLV-1-associated myelopathy. Unlike HTLV-1, the same group of retrovirus HTLV-2 has not been found to be associated with these diseases. HTLV-1 and HTLV-2 encode transforming proteins Tax1 and Tax2, and a few distinct activities of Tax1 from those of Tax2 have been proposed to contribute to the HTLV-1-specific pathogenesis of disease. One significant difference of Tax1 from Tax2 is the activation of transcription factor NF-κB2/p100/p52. We found that Tax1 but not Tax2 induces the expression of OX40 ligand (OX40L) in a human T-cell line. To induce the OX40L expression, Tax1 but not Tax2 was observed to interact with NF-κB2/p100/p52 and RelB and the distinct interaction activity was mediated by the Tax1 amino acid region of 225-232. In addition, Tax1 but not Tax2 or Tax1/225-232 interacted with p65, p50, and c-Rel; however, the interactions were much less than those noted with NF-κB2/p100/p52 and RelB. OX40L is a T-cell costimulatory molecule of the tumor necrosis factor family, and its signal plays a critical role in establishing adaptive immunity by inducing the polarized differentiation of T-cells to cells such as T helper type 2 and T follicular helper cells. Therefore, the present findings suggest that Tax1 might alter the immune response to HTLV-1 and/or differentiation of HTLV-1-infected T-cells via OX40L induction, thereby acting as a factor mediating the distinct phenotypes and pathogenesis of HTLV-1 from that of HTLV-2.
authors.affiliation: Divisions of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, 951-8510, Japan.|Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Motai
authors.affiliation: Divisions of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, 951-8510, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Division of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takachi
authors.affiliation: Divisions of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, 951-8510, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: Divisions of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, 951-8510, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hara
authors.affiliation: Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Mizuguchi
authors.affiliation: Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi
authors.affiliation: Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.affiliation: Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Divisions of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, 951-8510, Japan. fujiimas@med.niigata-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
mesh_terms: D016356:Gene Products, tax / Q000378:metabolism*; D057809:HEK293 Cells; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000502:physiology*; D015367:Human T-lymphotropic virus 2 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D052003:NF-kappa B p52 Subunit / Q000378:metabolism*; D053278:OX40 Ligand / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
chemical_list: D016356:Gene Products, tax; D052003:NF-kappa B p52 Subunit; D053278:OX40 Ligand; C514970:tax protein, Human T-lymphotrophic virus 1; C514971:tax protein, Human T-lymphotrophic virus 2; C000611828:tax2 protein, Human T-lymphotrophic virus 2
keywords: HTLV-1; NF-κB; OX40L; RelB; p52