Báo cáo y học: HTLV-I antisense transcripts initiating in the 3'LTR are alternatively spliced and polyadenylated

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Báo cáo y học: " HTLV-I antisense transcripts initiating in the 3LTR are alternatively spliced and polyadenylated"Retrovirology BioMed Central Open AccessResearchHTLV-I antisense transcripts initiating in the 3LTR arealternatively spliced and polyadenylatedMarie-Hélène Cavanagh1, Sébastien Landry1, Brigitte Audet1,Charlotte Arpin-André2, Patrick Hivin2, Marie-Ève Paré1, Julien Thête3,Éric Wattel3, Susan J Marriott4, Jean-Michel Mesnard*2 andBenoit Barbeau*1,5Address: 1Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, and Département de Biologiemédicale, Faculté de Médecine, Université Laval, Ste-Foy (Québec), G1V 4G2, Canada , 2Laboratoires Infections Rétrovirales et SignalisationCellulaire, CNRS/UM I UMR 5121/IFR 122, Institut de Biologie, 34960 Montpellier Cedex 2, France, 3Oncovirologie et Biothérapies, UMR5537CNRS-Université Claude Bernard, Centre Léon Berard and Service dHématologie, Pavillon E, Hôpital Edouard Herriot, Place dArsonval, Lyon,France, 4Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA and 5Université.du Québecà Montréal, Département des sciences biologiques, C.P. 8888, Succursale C.V., Montréal, Québec, H3C 3P8, CanadaEmail: Marie-Hélène Cavanagh - marie-helene.cavanagh@crchul.ulaval.ca; Sébastien Landry - sebastien.landry@crchul.ulaval.ca;Brigitte Audet - barbeau.benoit@uqam.ca; Charlotte Arpin-André - charlotte.arpin@univ-montp1.fr; Patrick Hivin - patrick.hivin@univ-montp1.fr; Marie-Ève Paré - barbeau.benoit@uqam.ca; Julien Thête - thete@lyon.fnclcc.fr; Éric Wattel - wattel@lyon.fnclcc.fr;Susan J Marriott - susanm@bcm.tmc.edu; Jean-Michel Mesnard* - jean-michel.mesnard@univ-montp1.fr;Benoit Barbeau* - barbeau.benoit@uqam.ca* Corresponding authorsPublished: 02 March 2006 Received: 23 December 2005 Accepted: 02 March 2006Retrovirology2006, 3:15 doi:10.1186/1742-4690-3-15This article is available from: http://www.retrovirology.com/content/3/1/15© 2006Cavanagh et al; licensee 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. Abstract Background: Antisense transcription in retroviruses has been suggested for both HIV-1 and HTLV-I, although the existence and coding potential of these transcripts remain controversial. Thorough characterization is required to demonstrate the existence of these transcripts and gain insight into their role in retrovirus biology. Results: This report provides the first complete characterization of an antisense retroviral transcript that encodes the previously described HTLV-I HBZ protein. In this study, we show that HBZ-encoding transcripts initiate in the 3 long terminal repeat (LTR) at several positions and consist of two alternatively spliced variants (SP1 and SP2). Expression of the most abundant HBZ spliced variant (SP1) could be detected in different HTLV-I-infected cell lines and importantly in cellular clones isolated from HTLV-I-infected patients. Polyadenylation of HBZ RNA occurred at a distance of 1450 nucleotides downstream of the HBZ stop codon in close proximity of a typical polyA signal. We have also determined that translation mostly initiates from the first exon located in the 3 LTR and that the HBZ isoform produced from the SP1 spliced variant demonstrated inhibition of Tax and c-Jun-dependent transcriptional activation. Conclusion: These results conclusively demonstrate the existence of antisense transcription in retroviruses, which likely plays a role in HTLV-I-associated pathogenesis through HBZ protein synthesis. Page 1 of 15 (page number not for citation purposes)Retrovirology 2006, 3:15 http://www.retrovirology.com ...