title: Heat Shock Enhances the Expression of the Human T Cell Leukemia Virus Type-I (HTLV-I) Trans-Activator (Tax) Antigen in Human HTLV-I Infected Primary and Cultured T Cells.
abstract: The environmental factors that lead to the reactivation of human T cell leukemia virus type-1 (HTLV-I) in latently infected T cells in vivo remain unknown. It has been previously shown that heat shock (HS) is a potent inducer of HTLV-I viral protein expression in long-term cultured cell lines. However, the precise HTLV-I protein(s) and mechanisms by which HS induces its effect remain ill-defined. We initiated these studies by first monitoring the levels of the trans-activator (Tax) protein induced by exposure of the HTLV-I infected cell line to HS. HS treatment at 43 °C for 30 min for 24 h led to marked increases in the level of Tax antigen expression in all HTLV-I-infected T cell lines tested including a number of HTLV-I-naturally infected T cell lines. HS also increased the expression of functional HTLV-I envelope gp46 antigen, as shown by increased syncytium formation activity. Interestingly, the enhancing effect of HS was partially inhibited by the addition of the heat shock protein 70 (HSP70)-inhibitor pifithlin-μ (PFT). In contrast, the HSP 70-inducer zerumbone (ZER) enhanced Tax expression in the absence of HS. These data suggest that HSP 70 is at least partially involved in HS-mediated stimulation of Tax expression. As expected, HS resulted in enhanced expression of the Tax-inducible host antigens, such as CD83 and OX40. Finally, we confirmed that HS enhanced the levels of Tax and gp46 antigen expression in primary human CD4⁺ T cells isolated from HTLV-I-infected humanized NOD/SCID/γc null (NOG) mice and HTLV-I carriers. In summary, the data presented herein indicate that HS is one of the environmental factors involved in the reactivation of HTLV-I in vivo via enhanced Tax expression, which may favor HTLV-I expansion in vivo.
authors.affiliation: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan. m-kunihiro@emro.co.jp.|EM Research Organization Inc., Okinawa, 901-2311, Japan. m-kunihiro@emro.co.jp.
authors.forename: Marie
authors.initials: M
authors.lastname: Kunihiro
authors.affiliation: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan. hfujii@med.u-ryukyu.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan. miya_skywalker2008@yahoo.co.jp.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyagi
authors.affiliation: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan. ytakah3@med.u-ryukyu.ac.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan. reiko_tanaka@s5.dion.ne.jp.
authors.forename: Reiko
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Laboratory of Hematoimmunology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan. fukutaku@med.u-ryukyu.ac.jp.
authors.forename: Takuya
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, 30322, USA. pathaaa@emory.edu.
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.affiliation: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan. yuetsu@s4.dion.ne.jp.
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015870:Gene Expression / Q000528:radiation effects*; D016356:Gene Products, tax / Q000096:biosynthesis*; D015490:HTLV-I Infections / Q000821:virology; D006358:Hot Temperature; D015368:Human T-lymphotropic virus 1 / Q000528:radiation effects*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000528:radiation effects* / Q000821:virology*
chemical_list: D016356:Gene Products, tax
keywords: HTLV-I; Tax; adult T cell leukemia (ATL); heat shock