{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T01:52:55Z","timestamp":1791078775523,"version":"4.1.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,7,19]]},"abstract":"<jats:p>\n                    Leukemogenic viruses like human T-lymphotropic virus and bovine leukemia virus (BLV) presumably persist in the host partly by latent integration of the provirus in a fraction of infected cells, leading to accumulative increase in the outgrowth of transformed cells. Furthermore, viral infection also correlates with a blockade of the apoptotic mechanisms concomitant with an apparent latency of the host cell. Conceptually, induction of viral or cellular gene expression could thus also be used as a therapeutic strategy against retroviral-associated leukemia. Here, we provide evidence that valproate, an inhibitor of deacetylases, activates BLV gene expression in transient transfection experiments and in short-term cultures of primary B-lymphocytes.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , valproate injection into newly BLV-inoculated sheep did not abrogate primary infection. However, valproate treatment, in the absence of any other cytotoxic drug, was efficient for leukemia\/lymphoma therapy in the sheep model leading to decreased lymphocyte numbers (respectively from 25.6, 35.7, and 46.5 \u00d7 10\n                    <jats:sup>3<\/jats:sup>\n                    cells per mm\n                    <jats:sup>3<\/jats:sup>\n                    to 1.0, 10.6, and 24.3 \u00d7 10\n                    <jats:sup>3<\/jats:sup>\n                    cells per mm\n                    <jats:sup>3<\/jats:sup>\n                    in three leukemic sheep) and tumor regression (from &gt;700 cm\n                    <jats:sup>3<\/jats:sup>\n                    to undetectable). The concept of a therapy that targets the expression of viral and cellular genes might be a promising treatment of adult T cell leukemia or tropical spastic paraparesis\/human T-lymphotropic virus-associated myelopathy, diseases for which no satisfactory treatment exists so far.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0504248102","type":"journal-article","created":{"date-parts":[[2005,7,9]],"date-time":"2005-07-09T00:01:18Z","timestamp":1120867278000},"page":"10309-10314","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":60,"title":["Valproate activates bovine leukemia virus gene expression, triggers apoptosis, and induces leukemia\/lymphoma regression\n                    <i>in vivo<\/i>"],"prefix":"10.1073","volume":"102","author":[{"given":"Amine","family":"Achachi","sequence":"first","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Florins","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Gillet","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Debacq","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Urbain","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germain Manfouo","family":"Foutsop","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Vandermeers","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Jasik","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Reichert","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Kerkhofs","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Lagneaux","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ars\u00e8ne","family":"Burny","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Kettmann","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Willems","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology, Gembloux University Faculty of Agronomic Sciences, 5030 Gembloux, Belgium; Department of Pathology, National Veterinary Research Institute, 24-100, Pulawy, Poland; Department of Virology, Veterinary and Agrochemical Research Center, 1180 Uccle, Belgium; and Jules Bordet Institute, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,7,8]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2002.18520.x"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.475"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/08892220050193326"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/08892220050193191"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3109\/13550289909015810"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm984"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.19334-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400009200"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570162033485203"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867033456576"},{"key":"e_1_3_2_11_2","first-page":"1017","volume":"20","year":"2000","unstructured":"Dressel, U., Renkawitz, R. & Baniahmad, A. (2000) Anticancer Res. 20, 1017-1022.10810390","journal-title":"Anticancer Res."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(03)02792-2"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206774"},{"key":"e_1_3_2_14_2","first-page":"1422","volume":"4","year":"2003","unstructured":"Secrist, J. P., Zhou, X. & Richon, V. M. (2003) Curr. Opin. Investig. Drugs 4, 1422-1427.14763127","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb05964.x"},{"key":"e_1_3_2_16_2","first-page":"269","volume":"5","year":"2003","unstructured":"Yoshida, M., Shimazu, T. & Matsuyama, A. (2003) Prog. Cell Cycle Res. 5, 269-278.14593721","journal-title":"Prog. Cell Cycle Res."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.10.5034-5042.2002"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.6969"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg315"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101287200"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867023369763"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(01)00151-5"},{"key":"e_1_3_2_23_2","first-page":"664","volume":"29","year":"2001","unstructured":"Wong, H., Rurak, D. W., Kumar, S., Kwan, E., Abbott, F. S. & Riggs, K. W. (2001) Drug Metab. Dispos. 29, 664-675.11302932","journal-title":"Drug Metab. Dispos."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2003.09.029"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204843200"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2126(80)90062-4"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.63.5.2099-2107.1989"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.1.630-639.1997"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-200320020-00005"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2003.41302.x"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-1-31"},{"key":"e_1_3_2_32_2","first-page":"759","volume":"7","year":"2001","unstructured":"Marks, P. A., Rifkind, R. A., Richon, V. M. & Breslow, R. (2001) Clin. Cancer Res. 7, 759-760.11309319","journal-title":"Clin. Cancer Res."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.10017"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.12.3847.h8003847_3847_3856"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2003.02097.x"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400371"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00095-8"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303740200"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00122-7"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104309200"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01081.x"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2003.07.013"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206502"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.65.3.520"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207315"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1160"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1161"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0504248102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T13:35:53Z","timestamp":1649770553000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0504248102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,7,8]]},"references-count":47,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2005,7,19]]}},"alternative-id":["10.1073\/pnas.0504248102"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0504248102","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,7,8]]},"assertion":[{"value":"2004-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-07-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}