{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:44:16Z","timestamp":1790477056899,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Livestock Promotional Subsidy from the Japan Racing Association"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bovine leukemia virus (BLV) causes enzootic bovine leukosis (EBL), yet its pathogenic mechanisms remain largely unclear. In particular, the role of BLV genomic integration sites (IS(s)) in BLV-induced leukemogenesis has not been fully elucidated. Here, we identified a total of 235 ISs from 99 BLV-infected cattle with lymphoma, of which 4.3% and 46.8% were located within exon and intron, respectively, while no preferential integration into CpG islands or repetitive regions was observed. All identified ISs were distinct, and no identical sites were detected among the samples. We identified 246 genes related with these ISs and protein\u2013protein interaction analysis of these genes demonstrated one \u201cIS-Clustered genes\u201d composed of 85 among 246 genes. This \u201cIS-Clustered genes\u201d contains 12 cancer genes (14.1%) with high significantly proportion. Notably, with 55 among 99 cattle tested (55.6%) harboring ISs within this cluster, suggesting its crucial involvement in BLV-induced pathogenesis. Furthermore, integrated analysis of known lymphoma- and IS-related genes and the 85 \u201cIS-Clustered genes\u201d showed that key genes formed a shared cluster, indicating a potential \u201ccommon EBL-associated cluster.\u201d These findings provide important insights into the role of BLV integration in EBL development and may contribute to elucidating its molecular mechanisms underlying onset of EBL. In addition, these findings may also aid in the development of therapeutic strategies and facilitate early diagnosis.<\/jats:p>","DOI":"10.3390\/ijms27020727","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T09:13:01Z","timestamp":1768209181000},"page":"727","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Diversity of Integration Sites of Bovine Leukemia Virus (BLV) and Roles of Genes Related to Development of BLV-Induced Lymphoma in a Large Cohort"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9487-9615","authenticated-orcid":false,"given":"Ryosuke","family":"Matsuura","sequence":"first","affiliation":[{"name":"Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, 1-1-1 Yayoi, Bunkyo-ku 113-8657, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9357-8795","authenticated-orcid":false,"given":"Meripet Polat","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, 1-1-1 Yayoi, Bunkyo-ku 113-8657, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0048-7212","authenticated-orcid":false,"given":"Noriko","family":"Fukushi","sequence":"additional","affiliation":[{"name":"Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, 1-1-1 Yayoi, Bunkyo-ku 113-8657, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Saito","sequence":"additional","affiliation":[{"name":"Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, 1-1-1 Yayoi, Bunkyo-ku 113-8657, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Fukumoto","sequence":"additional","affiliation":[{"name":"Support Unit for Bio-Material Analysis, Research Resources Division, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako 351-0198, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2712-1825","authenticated-orcid":false,"given":"Kazuyoshi","family":"Hosomichi","sequence":"additional","affiliation":[{"name":"Laboratory of Computational Genomics, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji 192-0392, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9648-0480","authenticated-orcid":false,"given":"Shin-nosuke","family":"Takeshima","sequence":"additional","affiliation":[{"name":"Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, 1-1-1 Yayoi, Bunkyo-ku 113-8657, Tokyo, Japan"},{"name":"Department of Food and Nutrition, Faculty of Human Life, Jumonji University, 2-1-28 Sugasawa, Niiza 352-8510, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7400-3587","authenticated-orcid":false,"given":"Yoko","family":"Aida","sequence":"additional","affiliation":[{"name":"Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, 1-1-1 Yayoi, Bunkyo-ku 113-8657, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Aida, Y., Murakami, H., Takahashi, M., and Takeshima, S.N. 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