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Blood, 17 September 2009, Vol. 114, No. 12, pp. 2427-2438. Prepublished online as a Blood First Edition Paper on July 14, 2009; DOI 10.1182/blood-2008-09-179879. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-09-179879v1 114/12/2427    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 CrossRef Google Scholar Articles by Halin, M. Articles by Mahieux, R. PubMed PubMed Citation Articles by Halin, M. Articles by Mahieux, R. Related Collections Immunobiology Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Human T-cell leukemia virus type 2 produces a spliced antisense transcript encoding a protein that lacks a classic bZIP domain but still inhibits Tax2-mediated transcription Marilène Halin1,*, Estelle Douceron25,*, Isabelle Clerc6, Chloé Journo25, Nga Ling Ko2, Sébastien Landry1, Edward L. Murphy7, Antoine Gessain2, Isabelle Lemasson8, Jean-Michel Mesnard6, Benoît Barbeau1,, and Renaud Mahieux25, 1 Département des Sciences Biologiques et Centre de recherche BioMed, Université du Québec à Montréal, Montreal, QC; 2 Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Centre National de la Recherche Scientifique Unité de Recherche Associée 3015, Département de Virologie, Institut Pasteur, Paris, France; 3 Equipe Oncogenèse Rétrovirale, Inserm U758 Virologie Humaine, Lyon, France; 4 Ecole Normale Supérieure de Lyon, Lyon, France; 5 Institut Fédératif de Recherche 128 Biosciences Lyon-Gerland, Lyon, France; 6 Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, Centre National de la Recherche Scientifique/UM1/UM2 Unité Mixte de Recherche 5236, Montpellier, France; 7 University of California, San Francisco and Blood Systems Research Institute, San Francisco; and 8 Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC Human T-cell leukemia virus type 1 (HTLV-1) and type 2 (HTLV-2) retroviruses infect T lymphocytes. The minus strand of the HTLV-1 genome encodes HBZ, a protein that could play a role in the development of leukemia in infected patients. Herein, we demonstrate that the complementary strand of the HTLV-2 genome also encodes a protein that we named APH-2 for "antisense protein of HTLV-2." APH-2 mRNA is spliced, polyadenylated, and initiates in the 3'-long terminal repeat at different positions. This transcript was detected in all HTLV-2–infected cell lines and short-term culture of lymphocytes obtained from HTLV-2 African patients tested and in 4 of 15 HTLV-2–infected blood donors. The APH-2 protein is 183 amino acids long, is localized in the cell nucleus, and is detected in vivo. Despite the lack of a consensus basic leucine zipper domain, APH-2 interacts with cyclic adenosine monophosphate-response element binding protein (CREB) and represses Tax2-mediated transcription in Tax2-expressing cells and in cells transfected with an HTLV-2 molecular clone. Altogether, our results demonstrate the existence of an antisense strand–encoded protein in HTLV-2, which could represent an important player in the development of disorders, such as lymphocytosis, which is frequently observed in HTLV-2 patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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