SEARCH:   Advanced

Blood, 15 November 2007, Vol. 110, No. 10, pp. 3722-3728. Prepublished online as a Blood First Edition Paper on August 23, 2007; DOI 10.1182/blood-2007-04-085076. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-04-085076v1 110/10/3722    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 Lezin, A. Articles by Willems, L. Search for Related Content PubMed PubMed Citation Articles by Lezin, A. Articles by Willems, L. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Histone deacetylase–mediated transcriptional activation reduces proviral loads in HTLV-1–associated myelopathy/tropical spastic paraparesis patients Agnès Lezin1, Nicolas Gillet2, Stéphane Olindo3, Aïssatou Signaté3, Nathalie Grandvaux4, Olivier Verlaeten2, Gildas Belrose1, Marcelo de Carvalho Bittencourt1, John Hiscott5, Becca Asquith6, Arsène Burny2, Didier Smadja3, Raymond Césaire1, and Luc Willems2 1 Laboratoire de Virologie-Immunologie and Jeune Equipe (JE) 2503, Centre Hospitalier Universitaire de Fort-de-France, Fort-de-France, Martinique, France; 2 Molecular and Cellular Biology, University Academia Wallonie-Europe, Gembloux, Belgium; 3 Service de Neurologie and Jeune Equipe (JE) 2503, Centre Hospitalier Universitaire de Fort-de-France, Fort-de-France, Martinique, France; 4 Département de Biochimie, Faculté de Médecine, Université de Montreal, Centre Hospitalier de l'Université de Montréal (CHUM)/Hôpital St Luc, Montreal, QC; 5 Molecular Oncology Group, Lady Davis Institute, Jewish General Hospital, Montreal, QC; and 6 Department of Immunology, Imperial College, London, United Kingdom Epigenetic modifications of chromatin may play a role in maintaining viral latency and thus persistence of the human T-lymphotropic virus type 1 (HTLV-1), which is responsible for HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A major determinant of disease progression is increased peripheral blood proviral load (PVL), possibly via the accumulation of infected cells in the central nervous system (CNS) creating a damaging inflammatory response. Current therapeutic approaches that focus on reducing either cell proliferation, viral replication, or tissue invasion are still unsatisfactory. Contrasting with these inhibitory strategies, we evaluated the efficacy of a novel approach aimed, paradoxically, at activating viral gene expression to expose virus-positive cells to the host immune response. We used valproate (VPA), a histone deacetylase inhibitor that has been used for decades as a chronic, safe treatment for epileptic disorders. Based on in vitro and in vivo data, we provide evidence that transient activation of the latent viral reservoir causes its collapse, a process that may alleviate the condition of HAM/TSP. This represents the first such approach to treating HAM/TSP, using gene activation therapy to tilt the host-pathogen balance in favor of an existing antiviral response. This trial is registered at http://clinicaltrials.gov/as no. NCT00519181 [ClinicalTrials.gov] . CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S A Cooper, M S. van der Loeff, and G P Taylor The neurology of HTLV-1 infection Practical Neurology, February 1, 2009; 9(1): 16 - 26. [Abstract] [Full Text] [PDF] R. Mahieux HTLV-I, Tax: fox hunting still allowed Blood, June 15, 2008; 111(12): 5418 - 5418. [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020