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; DOI: 10.1016/j.bbamcr.2013.03.006
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human T cell leukemia viruses (HTLVs) are complex human retroviruses of the Deltaretrovirus genus. Four types have been identified thus far, with HTLV-1 and HTLV-2 much more prevalent than HTLV-3 or HTLV-4. HTLV-1 and HTLV-2 possess strictly related genomic structures, but differ significantly in pathogenicity, as HTLV-1 is the causative agent of adult T cell leukemia and of HTLV-associated myelopathy/tropical spastic paraparesis, whereas HTLV-2 is not associated with neoplasia. HTLVs code for a protein named Tax that is responsible for enhancing viral expression and drives cell transformation. Much effort has been invested to dissect the impact of Tax on signal transduction pathways and to identify functional differences between the HTLV Tax proteins that may explain the distinct oncogenic potential of HTLV-1 and HTLV-2. This review summarizes our current knowledge of Tax-1 and Tax-2 with emphasis on their structure, role in activation of the NF-κB (nuclear factor kappa-B) pathway, and interactions with host factors.
    Frontiers in Microbiology 09/2013; 4:271. DOI:10.3389/fmicb.2013.00271 · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Immune injuries following the exposure of titanium dioxide nanoparticles (TiO2 NPs) have been greatly concerned along with the TiO2 NPs are widely used in pharmacology and daily life. However, very little is known about the immunomodulatory mechanisms in the spleen-injured mice due to TiO2 NPs exposure. In this study, mice were continuously exposed to 2.5, 5, or 10 TiO2 NPs mg kg(-1) body weight for 90 days with intragastric administration to investigate the immunomodulatory mechanisms in the spleen. The findings showed that TiO2 NPs exposure resulted in significant increases in spleen and thymus indices, and titanium accumulation, in turn led to histopathological changes and splenocyte apoptosis. Furthermore, the exposure of TiO2 NPs could significantly increase the levels of macrophage inflammatory protein (MIP)-1α, MIP-2, Eotaxin, monocyte chemotactic protein-1, interferon-γ, vascular cell adhesion molecule-1, interleukin-13, interferon-γ-inducible protein-10, migration inhibitory factor, CD69, major histocompatibility complex, protein tyrosine phosphatase, protein tyrosine kinase 1, basic fibroblast growth factor, Fasl, and GzmB expression, whereas markedly decrease the levels of NKG2D, NKp46, 2B4 expression involved in immune responses, lymphocyte healing and apoptosis. These findings would better understand toxicological effects induced by TiO2 NPs exposure. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
    Journal of Biomedical Materials Research Part A 11/2013; 102(10). DOI:10.1002/jbm.a.35034 · 2.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pathoepigenetics is a new discipline describing how disturbances in epigenetic regulation alter the epigenotype and gene expression pattern of human, animal or plant cells. Such 'epigenetic reprogramming' may play an important role in the initiation and progression of a wide variety of diseases. Infectious diseases also belong to this category: recent data demonstrated that microbial pathogens, including bacteria and viruses, are capable of dysregulating the epigenetic machinery of their host cell. The resulting heritable changes in host cell gene expression may favor colonization, growth or the spread of infectious pathogens. It may also facilitate the establishment of latency and malignant cell transformation. In this article, we review how bacterial epigenetic effectors and inflammatory processes elicited by bacteria alter the host cell epigenotype, and describe how oncoproteins encoded by human tumor viruses act as epigenetic dysregulators to alter the phenotype and behaviour of host cells.
    Future Virology 12/2013; 8(11):1-16. DOI:10.2217/fvl.13.97 · 1.00 Impact Factor