SEARCH:   Advanced

Blood, 1 December 2006, Vol. 108, No. 12, pp. 3801-3807. Prepublished online as a Blood First Edition Paper on August 15, 2006; DOI 10.1182/blood-2006-03-013235. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2006-03-013235v1 108/12/3801    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mosley, A. J. Articles by Bangham, C. R. Search for Related Content PubMed PubMed Citation Articles by Mosley, A. J. Articles by Bangham, C. R. Related Collections Immunobiology Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Histone deacetylase inhibitors increase virus gene expression but decrease CD8+ cell antiviral function in HTLV-1 infection Angelina Jane Mosley, Kiran N. Meekings, Corinna McCarthy, Dawn Shepherd, Vincenzo Cerundolo, Ralph Mazitschek, Yuetsu Tanaka, Graham P. Taylor, and Charles R. Bangham From the Department of Immunology, Wright Fleming Institute, and the Department of Genito-Urinary Medicine and Communicable Diseases, Imperial College London, United Kingdom; the Tumour Immunology Group, Weatherall Institute of Molecular Medicine, University of Oxford, United Kingdom; the Chemical Biology Program, Broad Institute of Harvard University and MIT, Cambridge, MA; and the Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Ryukyus, Japan. The dynamics of human T-lymphotropic virus type-1 (HTLV-1) provirus expression in vivo are unknown. There is much evidence to suggest that HTLV-1 gene expression is restricted: this restricted gene expression may contribute to HTLV-1 persistence by limiting the ability of the HTLV-1–specific CD8+ cell immune response to clear infected cells. In this study, we tested the hypothesis that derepression of HTLV-1 gene expression would allow an increase in CD8+ cell–mediated lysis of HTLV-1–infected cells. Using histone deacetylase enzyme inhibitors (HDIs) to hyperacetylate histones and increase HTLV-1 gene expression, we found that HDIs doubled Tax expression in naturally infected lymphocytes after overnight culture. However, the rate of CD8+ cell–mediated lysis of Tax-expressing cells ex vivo was halved. HDIs appeared to inhibit the CD8+ cell–mediated lytic process itself, indicating a role for the microtubule-associated HDAC6 enzyme. These observations indicate that HDIs may reduce the efficiency of cytotoxic T-cell (CTL) surveillance of HTLV-1 in vivo. The impact of HDIs on HTLV-1 proviral load in vivo cannot be accurately predicted because of the widespread effects of these drugs on cellular processes; we therefore recommend caution in the use of HDIs in nonmalignant cases of HTLV-1 infection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Toulza, A. Heaps, Y. Tanaka, G. P. Taylor, and C. R. M. Bangham High frequency of CD4+FoxP3+ cells in HTLV-1 infection: inverse correlation with HTLV-1-specific CTL response Blood, May 15, 2008; 111(10): 5047 - 5053. [Abstract] [Full Text] [PDF] A. Lezin, N. Gillet, S. Olindo, A. Signate, N. Grandvaux, O. Verlaeten, G. Belrose, M. de Carvalho Bittencourt, J. Hiscott, B. Asquith, et al. Histone deacetylase mediated transcriptional activation reduces proviral loads in HTLV-1 associated myelopathy/tropical spastic paraparesis patients Blood, November 15, 2007; 110(10): 3722 - 3728. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020