HTLV-1-Mediated Epigenetic Pathway to Adult T-Cell Leukemia–Lymphoma
Human T-cell leukemia virus type 1 (HTLV-1), the first reported human oncogenic retrovirus, is the etiologic agent of highly aggressive, currently incurable diseases such as adult T-cell leukemia–lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 proteins,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.01686/full |
| _version_ | 1798044801176698880 |
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| author | Makoto Yamagishi Dai Fujikawa Toshiki Watanabe Kaoru Uchimaru |
| author_facet | Makoto Yamagishi Dai Fujikawa Toshiki Watanabe Kaoru Uchimaru |
| author_sort | Makoto Yamagishi |
| collection | DOAJ |
| description | Human T-cell leukemia virus type 1 (HTLV-1), the first reported human oncogenic retrovirus, is the etiologic agent of highly aggressive, currently incurable diseases such as adult T-cell leukemia–lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 proteins, including Tax and HBZ, have been shown to have critical roles in HTLV-1 pathogenicity, yet the underlying mechanisms of HTLV-1-driven leukemogenesis are unclear. The frequent disruption of genetic and epigenetic gene regulation in various types of malignancy, including ATL, is evident. In this review, we illustrate a focused range of topics about the establishment of HTLV-1 memory: (1) genetic lesion in the Tax interactome pathway, (2) gene regulatory loop/switch, (3) disordered chromatin regulation, (4) epigenetic lock by the modulation of epigenetic factors, (5) the loss of gene fine-tuner microRNA, and (6) the alteration of chromatin regulation by HTLV-1 integration. We discuss the persistent influence of Tax-dependent epigenetic changes even after the disappearance of HTLV-1 gene expression due to the viral escape from the immune system, which is a remaining challenge in HTLV-1 research. The summarized evidence and conceptualized description may provide a better understanding of HTLV-1-mediated cellular transformation and the potential therapeutic strategies to combat HTLV-1-associated diseases. |
| first_indexed | 2024-04-11T23:10:09Z |
| format | Article |
| id | doaj.art-c4063224d4164712a050b871ae287af2 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-11T23:10:09Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-c4063224d4164712a050b871ae287af22022-12-22T03:57:53ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-07-01910.3389/fmicb.2018.01686384575HTLV-1-Mediated Epigenetic Pathway to Adult T-Cell Leukemia–LymphomaMakoto Yamagishi0Dai Fujikawa1Toshiki Watanabe2Kaoru Uchimaru3Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, JapanDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, JapanThe Institute of Medical Science, The University of Tokyo, Tokyo, JapanDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, JapanHuman T-cell leukemia virus type 1 (HTLV-1), the first reported human oncogenic retrovirus, is the etiologic agent of highly aggressive, currently incurable diseases such as adult T-cell leukemia–lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 proteins, including Tax and HBZ, have been shown to have critical roles in HTLV-1 pathogenicity, yet the underlying mechanisms of HTLV-1-driven leukemogenesis are unclear. The frequent disruption of genetic and epigenetic gene regulation in various types of malignancy, including ATL, is evident. In this review, we illustrate a focused range of topics about the establishment of HTLV-1 memory: (1) genetic lesion in the Tax interactome pathway, (2) gene regulatory loop/switch, (3) disordered chromatin regulation, (4) epigenetic lock by the modulation of epigenetic factors, (5) the loss of gene fine-tuner microRNA, and (6) the alteration of chromatin regulation by HTLV-1 integration. We discuss the persistent influence of Tax-dependent epigenetic changes even after the disappearance of HTLV-1 gene expression due to the viral escape from the immune system, which is a remaining challenge in HTLV-1 research. The summarized evidence and conceptualized description may provide a better understanding of HTLV-1-mediated cellular transformation and the potential therapeutic strategies to combat HTLV-1-associated diseases.https://www.frontiersin.org/article/10.3389/fmicb.2018.01686/fullHTLV-1ATLLepigeneticsEZH2gene expressiongene mutations |
| spellingShingle | Makoto Yamagishi Dai Fujikawa Toshiki Watanabe Kaoru Uchimaru HTLV-1-Mediated Epigenetic Pathway to Adult T-Cell Leukemia–Lymphoma Frontiers in Microbiology HTLV-1 ATLL epigenetics EZH2 gene expression gene mutations |
| title | HTLV-1-Mediated Epigenetic Pathway to Adult T-Cell Leukemia–Lymphoma |
| title_full | HTLV-1-Mediated Epigenetic Pathway to Adult T-Cell Leukemia–Lymphoma |
| title_fullStr | HTLV-1-Mediated Epigenetic Pathway to Adult T-Cell Leukemia–Lymphoma |
| title_full_unstemmed | HTLV-1-Mediated Epigenetic Pathway to Adult T-Cell Leukemia–Lymphoma |
| title_short | HTLV-1-Mediated Epigenetic Pathway to Adult T-Cell Leukemia–Lymphoma |
| title_sort | htlv 1 mediated epigenetic pathway to adult t cell leukemia lymphoma |
| topic | HTLV-1 ATLL epigenetics EZH2 gene expression gene mutations |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.01686/full |
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