{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:25:34Z","timestamp":1790699134420,"version":"4.1.0"},"reference-count":127,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000199","name":"United States Department of Agriculture","doi-asserted-by":"publisher","award":["2019-67011-29539\/1019321"],"award-info":[{"award-number":["2019-67011-29539\/1019321"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"United States Department of Agriculture","doi-asserted-by":"publisher","award":["2016-38420-25289"],"award-info":[{"award-number":["2016-38420-25289"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"United States Department of Agriculture","doi-asserted-by":"publisher","award":["2004-35204-17005"],"award-info":[{"award-number":["2004-35204-17005"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"United States Department of Agriculture","doi-asserted-by":"publisher","award":["2008-35204-04652"],"award-info":[{"award-number":["2008-35204-04652"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"United States Department of Agriculture","doi-asserted-by":"publisher","award":["W3112 Reproduction in Domestic Ruminants HATCH project #1011648"],"award-info":[{"award-number":["W3112 Reproduction in Domestic Ruminants HATCH project #1011648"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Bovine viral diarrhea virus (BVDV) infection during early gestation results in persistently infected (PI) immunotolerant calves that are the primary reservoirs of the virus. Pathologies observed in PI cattle include congenital defects of the brain, heart, and bone as well as marked functional defects in their immune system. It was hypothesized that fetal BVDV infection alters T cell activation and signaling genes by epigenetic mechanisms. To test this, PI and control fetal splenic tissues were collected on day 245 of gestation, 170 days post maternal infection. DNA was isolated for reduced representation bisulfite sequencing, protein was isolated for proteomics, both were analyzed with appropriate bioinformatic methods. Within set parameters, 1951 hypermethylated and 691 hypomethylated DNA regions were identified in PI compared to control fetuses. Pathways associated with immune system, neural, cardiac, and bone development were associated with heavily methylated DNA. The proteomic analysis revealed 12 differentially expressed proteins in PI vs. control animals. Upregulated proteins were associated with protein processing, whereas downregulated proteins were associated with lymphocyte migration and development in PI compared to control fetal spleens. The epigenetic changes in DNA may explain the immune dysfunctions, abnormal bone formation, and brain and heart defects observed in PI animals.<\/jats:p>","DOI":"10.3390\/v14030506","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T20:11:57Z","timestamp":1646079117000},"page":"506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Epigenomic and Proteomic Changes in Fetal Spleens Persistently Infected with Bovine Viral Diarrhea Virus: Repercussions for the Developing Immune System, Bone, Brain, and Heart"],"prefix":"10.3390","volume":"14","author":[{"given":"Hanah","family":"Georges","sequence":"first","affiliation":[{"name":"Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Van Campen","sequence":"additional","affiliation":[{"name":"Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helle","family":"Bielefeldt-Ohmann","sequence":"additional","affiliation":[{"name":"Australian Infections Diseases Research Centre, The University of Queensland, St. Lucia, QLD 4072, Australia"},{"name":"School of Chemistry & Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hansen","sequence":"additional","affiliation":[{"name":"Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"ref_1","first-page":"205","article-title":"An apparently new transmissible disease of cattle","volume":"36","author":"Olafson","year":"1946","journal-title":"Cornell Veter."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.cvfa.2009.10.007","article-title":"Bovine Viral Diarrhea Virus: Global Status","volume":"26","author":"Ridpath","year":"2010","journal-title":"Vet. 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