{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:33:43Z","timestamp":1791916423293,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012659","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000}}],"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["FNRS PDR T.O261.20, PER H.P055.20, CDR J.0195.21, and J.0194.23"],"award-info":[{"award-number":["FNRS PDR T.O261.20, PER H.P055.20, CDR J.0195.21, and J.0194.23"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"name":"T\u00e9l\u00e9vie","award":["7460621 and 7460923"],"award-info":[{"award-number":["7460621 and 7460923"]}]},{"DOI":"10.13039\/501100005627","name":"Universit\u00e9 de Li\u00e8ge","doi-asserted-by":"crossref","award":["FSR-S-SS-2023\/14"],"award-info":[{"award-number":["FSR-S-SS-2023\/14"]}],"id":[{"id":"10.13039\/501100005627","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006673","name":"Fonds L\u00e9on Fredericq","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006673","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>In sheep infected with bovine leukemia virus (BLV), transcription of structural, enzymatic, and accessory genes is silenced. However, the BLV provirus transcribes a series of non-coding RNAs that remain undetected by the host immune response. Specifically, three RNAs (AS1-L, AS1-S, and AS2) are consistently expressed from the antisense strand, originating from transcriptional initiation at the 3\u2019-Long Terminal Repeat (LTR). To investigate the role of these non-coding RNAs in viral replication and pathogenesis, a reverse genetics approach was devised, capitalizing on a mechanistic disparity in transcription initiation between the 5\u2019 and 3\u2019 promoters. A two-nucleotide mutation (GG&gt;TA) in the TFIIB-recognition element (BRE) impaired antisense transcription originating from the 3\u2019-LTR. In the context of the provirus, this 2bp mutation significantly diminished the expression of antisense RNAs, while not notably affecting sense transcription. When inoculated to sheep, the mutated provirus was infectious but exhibited reduced replication levels, shedding light on the role of antisense transcription in vivo. In comparison to lymphoid organs in sheep infected with a wild-type (WT) provirus, the mutant demonstrated alterations in both the spatial distribution and rates of cell proliferation in the lymph nodes and the spleen. Analysis through RNA sequencing and RT-qPCR unveiled an upregulation of the <jats:italic>Hmcn1\/<\/jats:italic>hemicentin-1 gene in B-lymphocytes from sheep infected with the mutated provirus. Further examination via confocal microscopy and immunohistochemistry revealed an increase in the amount of hemicentin-1 protein encoded by <jats:italic>Hmcn1<\/jats:italic> in peripheral blood mononuclear cells (PBMCs) and lymphoid organs of sheep infected with the mutant. RNA interference targeting <jats:italic>Hmcn1<\/jats:italic> expression impacted the migration of ovine kidney (OVK) cells <jats:italic>in vitro<\/jats:italic>. In contrast to the WT, the mutated provirus showed reduced oncogenicity when inoculated into sheep. Collectively, this study underscores the essential role of antisense transcription in BLV replication and pathogenicity. These findings may offer valuable insights into understanding the relevance of antisense transcription in the context of human T-cell leukemia virus (HTLV-1).<\/jats:p>","DOI":"10.1371\/journal.ppat.1012659","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T18:42:16Z","timestamp":1731004936000},"page":"e1012659","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Reduction of antisense transcription affects bovine leukemia virus replication and oncogenesis"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0813-0259","authenticated-orcid":true,"given":"Thomas","family":"Joris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1323-779X","authenticated-orcid":true,"given":"Thomas","family":"Jouant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Rock","family":"Jacques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorian","family":"Gouverneur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Saintmard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Vilanova Ma\u00f1\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majeed","family":"Jamakhani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Reichert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-2213","authenticated-orcid":true,"given":"Luc","family":"Willems","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"ppat.1012659.ref001","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0378-1135(01)00458-8","article-title":"Vertical transmission of bovine leukemia virus and bovine immunodeficiency virus in dairy cattle herds","volume":"84","author":"S. 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