CD69 overexpression by human T-cell leukemia virus type 1 Tax transactivation

Department of Microbiology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
Biochimica et Biophysica Acta (Impact Factor: 4.66). 03/2013; 1833(6). DOI: 10.1016/j.bbamcr.2013.03.006
Source: PubMed


Human T-cell leukemia virus type 1 (HTLV-1) infection is associated with the development of adult T-cell leukemia (ATL) and various inflammatory diseases. CD69 is a marker of early activation of lymphocytes. We investigated the effects of HTLV-1 infection on the expression of CD69. The CD69 gene was upregulated in all viral protein Tax-expressing HTLV-1-transformed T-cell lines, except MT-2 and peripheral blood mononuclear cells (PBMCs) from patients with ATL compared with uninfected T-cell line, Tax-negative ATL-derived T-cell lines and normal PBMCs. Flow cytometric analysis and immunohistochemical analysis confirmed the enhanced expression of CD69 in HTLV-1-transformed T-cell lines and in ATL cells in lymph nodes and skin lesions, and its absence in MT-2 and PBMCs. CD69 expression was induced following infection of human T-cell line with HTLV-1, and specifically by Tax. Tax transcriptionally activated CD69 gene through both nuclear factor-κB (NF-κB) and cyclic adenosine 3',5'-monophosphate response element-binding protein signaling pathways. Detailed analysis of the CD69 promoter indicated that the Tax-induced expression of CD69 was regulated by multiple cis-acting elements and by the interplay of transcription factors of the NF-κB, early growth response and cyclic adenosine 3',5'-monophosphate response element-binding protein families. The lack of CD69 expression in MT-2 is due to epigenetic mechanism involving deacetylation, but not methylation. We conclude that CD69 is a Tax-regulated gene, and its regulation by Tax may play a role in cellular activation and HTLV-1-induced disease pathogenesis.

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Available from: Masachika Senba, Jul 01, 2015
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    • "Kim et al. (2008) provided evidence that Tax-1 induces Bcl-3 expression primarily through activation of the NF-κB pathway. Another recent study has demonstrated that Tax-1 transactivates CD69, a marker of early activation of lymphocytes, through both NF-κB and CREB signaling pathways (Ishikawa et al., 2013). Tax-1-mediated activation of the non-canonical NF-κB pathway is important in virus-induced tumorigenesis. "
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    • "The early activation antigen CD69 is a type I1 integral membrane glycoprotein included in the natural killer cell gene complex family of signal transducing receptors [44–46]. CD69 represents one of the earliest activation markers of T lymphocytes appearing within 1–2 h after stimulation [47, 48]. Consequently, CD69 expression has been used as a marker of T cell activation both in vivo and in vitro [49–51]. "
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