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

• Authors: Marie Kunihiro, University of the Ryukyus; Hideki Fujii, University of the Ryukyus; Takuya Miyagi, University of the Ryukyus; Yoshiaki Takahashi, University of the Ryukyus; Reiko Tanaka, University of the Ryukyus; Takuya Fukushima, University of the Ryukyus; Aftab Ansari, Emory University; Yuetsu Tanaka, University of the Ryukyus
• Journal Title: Viruses
• Volume: Volume 8, Number 7
• Publisher: MDPI | 2016-07-11, Pages 191-191
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3390/v8070191
• Subjects: Health Sciences, Immunology; Biology, Cell; Biology, Virology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Virology; HTLV-I; Tax; heat shock; adult T cell leukemia (ATL); MONOCLONAL-ANTIBODIES; STRESS-RESPONSE; GENE-EXPRESSION; ENVELOPE GP46; PROTEIN; HSP70; REPLICATION; LYMPHOCYTES; ACTIVATION; LINES

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.