{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:25:36Z","timestamp":1790699136456,"version":"4.1.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Persistently infected (PI) calves resulting from maternal Bovine viral diarrhea virus (BVDV) infection during early gestation are the main source of viral transmission and pose a serious threat to the sustainable production of herds. PI cattle appear clinically normal, elucidating the molecular-level alterations is critical for understanding their specific characteristics. Moreover, the identification of candidate biomarkers for diagnosing PI cattle will provide valuable insights to support effective strategies for the control and eventual eradication of BVDV. At the same time, few studies have focused on the mothers of PI calves (Trojan dam).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated RNA-seq and reduced representation bisulfite sequencing (RRBS) to characterize the molecular features of PI calves and Trojan dams and identified DNA methylation biomarkers in PI calves.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In this study, we found that both B cell and T cell receptor signaling pathways were less active in PI calves, along with a significantly reduced B cell proportion compared to normal calves. By integrating transcriptome and methylation data, we found that the elevated expression of\n                      <jats:italic>MAPK13<\/jats:italic>\n                      and\n                      <jats:italic>LSP1<\/jats:italic>\n                      in PI calves is potentially regulated by promoter methylation. Furthermore, we identified a potential ZBTB38\u2013methylation\u2013MAPK13 regulatory axis influencing downstream genes such as\n                      <jats:italic>IL1B<\/jats:italic>\n                      ,\n                      <jats:italic>KDR<\/jats:italic>\n                      ,\n                      <jats:italic>FOSB<\/jats:italic>\n                      , and\n                      <jats:italic>PTGS2<\/jats:italic>\n                      , which may collectively impact the physiological state of PI calves. In Trojan dams and normal dams, we identified a total of eight genes potentially regulated by DNA methylation, including\n                      <jats:italic>KLHL33<\/jats:italic>\n                      ,\n                      <jats:italic>KLRG1<\/jats:italic>\n                      ,\n                      <jats:italic>NQO2<\/jats:italic>\n                      and etc. By comparing PI calves with Trojan dams, normal calves, and normal dams, we identified a differentially methylated region (DMR) located in the\n                      <jats:italic>PES1<\/jats:italic>\n                      gene that was specifically hypomethylated in PI calves but hypermethylated in the other groups, suggesting its potential as a candidate diagnostic biomarker for PI detection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study revealed that the immune system of PI cattle is already compromised and identified a novel candidate diagnostic biomarker, providing a new perspective for the detection of PI cattle. In addition, we reveal that prenatal BVDV exposure induces persistent DNA methylation alterations in Trojan dams.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1763258","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:29:27Z","timestamp":1773120567000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive methylome and transcriptome profiling reveals specific biomarkers for bovine viral diarrhea virus persistent infection in calves"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiahao","family":"Wang","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Animal Breeding, State Key Laboratory of Animal Biotech Breeding, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University","place":["Beijing, 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China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Qin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Biosafety Risk Prevention and Control (North) & Key Laboratory of Veterinary Biological Products and Chemical Drugs of MARA, Institute of Animal Science, Chinese Academy of Agricultural Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University","place":["Beijing, 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