Volume 11 Supplement 1

16th International Conference on Human Retroviruses: HTLV and Related Viruses

Open Access

HTLV-1 Tax disrupts the host epigenome by interacting with a Polycomb group protein EZH2

  • Dai Fujikawa1,
  • Makoto Yamagishi1,
  • Naoya Kurokawa1,
  • Ai Soejima1,
  • Takaomi Ishida2,
  • Yuetsu Tanaka3,
  • Kazumi Nakano1 and
  • Toshiki Watanabe1Email author
Retrovirology201411(Suppl 1):P144

https://doi.org/10.1186/1742-4690-11-S1-P144

Published: 7 January 2014

ATL is a highly aggressive T-cell neoplasm caused by HTLV-1. We have recently demonstrated that EZH2, a catalytic enzyme of histone H3K27 methylation, is overexpressed in ATL cells, which contributes to persistent NF-κB activation by repressing a tumor-suppressive miRNA, miR-31. This suggests that epigenetic abnormalities are closely associated with the molecular hallmarks of leukemic cells. However, the mechanisms by which epigenetic disruption is caused and sustained in HTLV-1 infected cells remain to be clarified. In the present study, we first found that Tax directly interacts with EZH2 in HTLV-1 infected cells. Given that epigenetic state is directly affected by cell lineage-dependent transcription factors and genetic background, we assessed the functional interconnection between HTLV-1 Tax and the histone methyltransferases in an appropriate model. Using a lentivirus vector, we introduced tax gene into peripheral blood mononuclear cells (PBMCs) and CD4+ T-cells from healthy donors and established Tax-transduced T-cells. In this model, we observed overexpression of EZH2, aberrant accumulation of H3K27 trimethylation, and epigenetic silencing of p21 cip1/waf1 , all of which have been observed in primary ATL cells. In addition, EZH2 inhibition reduced the viability of Tax-transduced T-cells. Our results strongly suggest that Tax epigenetically affects gene expression through its interaction with EZH2, and that Tax-dependent epigenetic abnormalities may be involved in determining the molecular characteristics of HTLV-1-infected cells as well as ATL cells. Since epigenetic marks are potentially reversible, development of genuine epigenetic-targeted drugs will hold great promise in treatment of HTLV-1-related diseases.

Authors’ Affiliations

(1)
Graduate School of Frontier Sciences, The University of Tokyo
(2)
Institute of Medical Science, The University of Tokyo
(3)
Graduate School and Faculty of Medicine, University of the Ryukyus

Copyright

© Fujikawa et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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