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Viruses 2016, 8(7), 191; doi:10.3390/v8070191

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

1
Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan
2
EM Research Organization Inc., Okinawa, 901-2311, Japan
3
Laboratory of Hematoimmunology, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Okinawa, 903-0215, Japan
4
Department of Pathology, Emory University School of Medicine, Atlanta, GA, 30322, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Louis Mansky
Received: 21 April 2016 / Revised: 24 June 2016 / Accepted: 1 July 2016 / Published: 11 July 2016
(This article belongs to the Special Issue Recent Advances in HTLV Research 2015)
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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. View Full-Text
Keywords: HTLV-I; Tax; heat shock; adult T cell leukemia (ATL) HTLV-I; Tax; heat shock; adult T cell leukemia (ATL)
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MDPI and ACS Style

Kunihiro, M.; Fujii, H.; Miyagi, T.; Takahashi, Y.; Tanaka, R.; Fukushima, T.; Ansari, A.A.; Tanaka, Y. 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. Viruses 2016, 8, 191.

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