{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T09:48:42Z","timestamp":1782208122201,"version":"3.54.5"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Animal Genetics"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bovine leukemia virus (BLV), an oncogenic deltaretrovirus, establishes lifelong infection in cattle and induces enzootic bovine leukosis in a subset of animals following prolonged latency. Despite extensive evidence of immune dysregulation, stage\u2010specific transcriptional reprogramming of B cells, the primary viral reservoir remains incompletely understood. In this study, we performed a targeted RNA\u2010sequencing analysis to characterize B\u2010cell\u2013associated transcriptional profiles across three clinical stages: uninfected controls (CT), asymptomatic BLV\u2010infected cattle (AC), and persistent lymphocytosis (PL). Differential gene expression analysis revealed a dynamic, stage\u2010dependent remodeling of B\u2010cell immune functions. Asymptomatic infection was characterized by significant upregulation of key B\u2010cell receptor (BCR) signaling components, including\n                    <jats:italic>CD79B<\/jats:italic>\n                    and\n                    <jats:italic>SYK<\/jats:italic>\n                    , alongside increased expression of major histocompatibility complex class II genes (\n                    <jats:italic>BoLA\u2010DRA, BoLA\u2010DRB3<\/jats:italic>\n                    ) and immunoglobulin assembly gene\n                    <jats:italic>JCHAIN<\/jats:italic>\n                    , indicating enhanced antigen responsiveness and partial activation of antibody\u2010related pathways. However, transcriptional regulators of terminal plasma cell differentiation (\n                    <jats:italic>PRDM1<\/jats:italic>\n                    and\n                    <jats:italic>XBP1<\/jats:italic>\n                    ) remained unchanged, suggesting incomplete maturation. In contrast, progression to persistent lymphocytosis was associated with attenuation of canonical BCR signaling and reduced expression of antigen presentation and immunoglobulin assembly genes relative to the asymptomatic stage. Notably, germinal center\u2013associated transcription factors (\n                    <jats:italic>BCL6, AICDA, RGS13, MEF2B<\/jats:italic>\n                    ) remained largely unchanged across all comparisons, indicating that BLV\u2010driven lymphomagenesis does not resemble a classical germinal center\u2013derived process. Collectively, these findings support a biphasic model of BLV\u2010induced B\u2010cell modulation, characterized by early immune activation followed by functional reprogramming and immune attenuation during disease progression. This stage\u2010dependent remodeling provides new mechanistic insights into BLV pathogenesis and B\u2010cell transformation.\n                  <\/jats:p>","DOI":"10.1002\/age.70136","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:51:03Z","timestamp":1780671063000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stage\u2010Dependent Transcriptional Reprogramming of B\u2010Cell Receptor Signaling and Antigen Presentation During Bovine Leukemia Virus\u2013Driven Lymphomagenesis"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1583-891X","authenticated-orcid":false,"given":"Mohammad Mehdi","family":"Akbarin","sequence":"first","affiliation":[{"name":"Virology, Genetics, and Molecular Biology Laboratory, Faculty of Higher Studies Cuautitlan, Veterinary Medicine, Campus 4 National Autonomous University of Mexico  Cuautitlan Izcalli Mexico"},{"name":"Mashhad Medical Sciences\u2010Medical School Islamic Azad University  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Farjami","sequence":"additional","affiliation":[{"name":"Virology, Genetics, and Molecular Biology Laboratory, Faculty of Higher Studies Cuautitlan, Veterinary Medicine, Campus 4 National Autonomous University of Mexico  Cuautitlan Izcalli Mexico"},{"name":"Department of Biology, Damghan Branch Islamic Azad University  Damghan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia Rodr\u00edguez","family":"Murillo","sequence":"additional","affiliation":[{"name":"Virology, Genetics, and Molecular Biology Laboratory, Faculty of Higher Studies Cuautitlan, Veterinary Medicine, Campus 4 National Autonomous University of Mexico  Cuautitlan Izcalli Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor David","family":"Gonz\u00e1lez\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Virology, Genetics, and Molecular Biology Laboratory, Faculty of Higher Studies Cuautitlan, Veterinary Medicine, Campus 4 National Autonomous University of Mexico  Cuautitlan Izcalli Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Eduardo","family":"Acevedo\u2010Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Virology, Genetics, and Molecular Biology Laboratory, Faculty of Higher Studies Cuautitlan, Veterinary Medicine, Campus 4 National Autonomous University of Mexico  Cuautitlan Izcalli Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucero","family":"de Mar\u00eda \u00c1vila\u2010De la Vega","sequence":"additional","affiliation":[{"name":"Virology, Genetics, and Molecular Biology Laboratory, Faculty of Higher Studies Cuautitlan, Veterinary Medicine, Campus 4 National Autonomous University of Mexico  Cuautitlan Izcalli Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1682-8104","authenticated-orcid":false,"given":"Hugo Ram\u00edrez","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Virology, Genetics, and Molecular Biology Laboratory, Faculty of Higher Studies Cuautitlan, Veterinary Medicine, Campus 4 National Autonomous University of Mexico  Cuautitlan Izcalli Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.148"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-025-11216-5"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.07.009"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-023-07061-4"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2021.105153"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3814"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00222"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1113"},{"key":"e_1_2_16_10_1","first-page":"1","article-title":"Phylogenetic and Mutational Analysis of Bovine Leukemia Virus (BLV) Tax Gene in Specialized Dairy Production Systems in Antioquia, Colombia","volume":"61","author":"Castillo\u2010Rey D.","year":"2025","journal-title":"Veterinaria Italiana"},{"key":"e_1_2_16_11_1","first-page":"457","article-title":"Molecular Detection of Bovine Leukosis Virus in Naturally Infected Dairy and Dual\u2010Purpose Cattle in Mexico","volume":"14","author":"Cordero\u2010Pulido R. 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