{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:57:22Z","timestamp":1792789042180,"version":"4.5.0"},"reference-count":65,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["21H02357"],"award-info":[{"award-number":["21H02357"]}]},{"name":"JSPS KAKENHI","award":["23K21269"],"award-info":[{"award-number":["23K21269"]}]},{"name":"JSPS Invitational Fellowships for Research in Japan","award":["718H202418"],"award-info":[{"award-number":["718H202418"]}]},{"name":"Hirose Foundation","id":[{"id":"https:\/\/ror.org\/05tr29253","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05tr29253","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Kobayashi Foundation"},{"id":[{"id":"https:\/\/ror.org\/05501m963","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Bovine leukemia virus (BLV) is an oncogenic retrovirus responsible for enzootic bovine leukosis (EBL) in cattle. Previous studies indicated that increased levels of the miRNA hsa-miR-424-5p in milk small extracellular vesicles (sEVs) may serve as an EBL biomarker in cattle; however, its alteration across the clinical stages of BLV infection to the onset of EBL remains unclear. This study evaluated the prognostic potential of hsa-miR-424-5p in milk sEVs across distinct clinical stages of BLV infection to EBL onset. qPCR analysis showed that the abundance of hsa-miR-424-5p was lower in milk sEVs from BLV-infected cattle with low and high proviral load (LPVL and HPVL) compared to BLV-uninfected healthy cattle (Control), but was not significant (p &gt; 0.05). In contrast, the abundance of hsa-miR-424-5p in milk sEVs was significantly higher in EBL cattle than in the Control and HPVL cattle (p &lt; 0.05). Spearman\u2019s correlation analysis revealed a significant inverse association between hsa-miR-424-5p and the percentage of lactate dehydrogenase 2 + 3 (r = \u22120.28, p &lt; 0.001), whereas no significant correlations were observed with other parameters. hsa-miR-424-5p showed the highest discriminative performance in distinguishing BLV-infected cattle from EBL cattle (area under the curve [AUC] = 0.71), followed by Control vs. BLV (AUC = 0.63), indicating statistically meaningful biomarker utility across disease stages. These findings suggest that the amount of hsa-miR-424-5p in milk sEVs increases during the progression from the late stage of BLV infection to EBL onset, demonstrating that hsa-miR-424-5p may serve as a part of the biomarker panel for monitoring BLV progression and predicting EBL onset.<\/jats:p>","DOI":"10.3390\/ani16192976","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:17:54Z","timestamp":1790065074000},"page":"2976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Stage-Specific Alteration of hsa-miR-424-5p in Milk Small Extracellular Vesicles from Bovine Leukemia Virus Infection to Progression of Enzootic Bovine Leukosis"],"prefix":"10.3390","volume":"16","author":[{"given":"Md. Matiur","family":"Rahman","sequence":"first","affiliation":[{"name":"Laboratory of Food and Environmental Hygiene, Joint Department of Veterinary Medicine, Gifu University, Gifu 501-1193, Japan"},{"name":"Department of Medicine, Faculty of Veterinary, Animal and Biomedical Sciences, Sylhet Agricultural University, Sylhet 3100, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Moriyasu","sequence":"additional","affiliation":[{"name":"Laboratory of Food and Environmental Hygiene, Joint Department of Veterinary Medicine, Gifu University, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9573-5162","authenticated-orcid":false,"given":"Yuji O.","family":"Kamatari","sequence":"additional","affiliation":[{"name":"Institute for Glyco-Core Research (iGCORE), Gifu University, Gifu 501-1193, Japan"},{"name":"The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan"},{"name":"Division of Instrumental Analysis, Life Science Research Center, Gifu University, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7290-2482","authenticated-orcid":false,"given":"Ayaka","family":"Okada","sequence":"additional","affiliation":[{"name":"Laboratory of Food and Environmental Hygiene, Joint Department of Veterinary Medicine, Gifu University, Gifu 501-1193, Japan"},{"name":"Education and Research Center for Food Animal Health, Gifu University (GeFAH), Gifu 501-1193, Japan"},{"name":"Joint Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1189-8392","authenticated-orcid":false,"given":"Yasuo","family":"Inoshima","sequence":"additional","affiliation":[{"name":"Laboratory of Food and Environmental Hygiene, Joint Department of Veterinary Medicine, Gifu University, Gifu 501-1193, Japan"},{"name":"Education and Research Center for Food Animal Health, Gifu University (GeFAH), Gifu 501-1193, Japan"},{"name":"Joint Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref_1","unstructured":"King, A.M.Q., Lefkowitz, E., Adams, M.J., and Carstens, E.B. 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