Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus
Abstract Background Bovine viral diarrhea virus (BVDV) is the most detrimental pestivirus within the cattle industry. Infection with vertically transmissible BVDV prior to 125 days of gestation results in the generation of a persistently infected (PI) calf. These PI calves are unable to clear the vi...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12864-025-11562-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849314833093099520 |
|---|---|
| author | Jessica N. Kincade Terry E. Engle Marcela Henao-Tamayo Jordan M. Eder Erin M. McDonald Darcy M. Deines Brie M. Wright Dilyara Murtazina Jeanette V. Bishop Thomas R. Hansen Hana Van Campen |
| author_facet | Jessica N. Kincade Terry E. Engle Marcela Henao-Tamayo Jordan M. Eder Erin M. McDonald Darcy M. Deines Brie M. Wright Dilyara Murtazina Jeanette V. Bishop Thomas R. Hansen Hana Van Campen |
| author_sort | Jessica N. Kincade |
| collection | DOAJ |
| description | Abstract Background Bovine viral diarrhea virus (BVDV) is the most detrimental pestivirus within the cattle industry. Infection with vertically transmissible BVDV prior to 125 days of gestation results in the generation of a persistently infected (PI) calf. These PI calves are unable to clear the virus in utero, due to an incomplete immune response. However, when infection with BVDV occurs after 150 days of gestation, the fetus clears the transient infection (TI) in utero and is born with antibodies specific to the infecting strain of BVDV. Variations in DNA methylation have been identified in white blood cells (WBC) from TI heifers at birth. It was hypothesized that epigenomic alterations persist into the postnatal period and contribute to previously undocumented pathologies. To study these possible effects, DNA was isolated from the WBCs of 5 TI heifers and 5 control heifers at 4 months of age and subjected to reduced representation bisulfite sequencing (RRBS). Results Differential analysis of the methylome revealed a total of 3,047 differentially methylated CpG sites (DMSs), 1,349 of which were hypermethylated and the other 1,698 were hypomethylated. Genes containing differential methylation were associated with inflammation, reactive oxygen species (ROS) production, and metabolism. Complete blood count (CBC) data identified a higher lymphocyte percentage in TI heifers. When compared in the context of the CD45+ parent population, spectral flow cytometry revealed increased intermediate monocytes, B cells, and CD25+/CD127− T cells, and decreased CD4+/CD8b+ T cells. Comparative analysis revealed differential methylation of CpG sites contained in 205 genes, 5 promoters, and 10 CpG islands at birth that were also present at 4 months of age. Comparison of differential methylation in TI heifers and PI heifers at 4 months of age showed 465 genes, 18 promoters, and 34 CpG islands in common. Conclusion Differential methylation of WBC DNA persists to 4 months of age in TI heifers and is associated with dysregulation of inflammation, metabolism, and growth. Analysis of differential methylation in TI heifers contributes to the understanding of how fetal infection with BVDV induces postnatal detriments related to profit loss. |
| format | Article |
| id | doaj-art-ca0b3ba913dc433195bb2893efebc8c8 |
| institution | Kabale University |
| issn | 1471-2164 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj-art-ca0b3ba913dc433195bb2893efebc8c82025-08-20T03:52:19ZengBMCBMC Genomics1471-21642025-05-0126112210.1186/s12864-025-11562-5Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virusJessica N. Kincade0Terry E. Engle1Marcela Henao-Tamayo2Jordan M. Eder3Erin M. McDonald4Darcy M. Deines5Brie M. Wright6Dilyara Murtazina7Jeanette V. Bishop8Thomas R. Hansen9Hana Van Campen10Department of Biomedical Sciences, Colorado State UniversityDepartment of Animal Sciences, Colorado State UniversityDepartment of Microbiology, Immunology, and Pathology, Colorado State UniversityResearch Innovation CenterResearch Innovation CenterResearch Innovation CenterResearch Innovation CenterDepartment of Biomedical Sciences, Colorado State UniversityDepartment of Biomedical Sciences, Colorado State UniversityDepartment of Biomedical Sciences, Colorado State UniversityDepartment of Biomedical Sciences, Colorado State UniversityAbstract Background Bovine viral diarrhea virus (BVDV) is the most detrimental pestivirus within the cattle industry. Infection with vertically transmissible BVDV prior to 125 days of gestation results in the generation of a persistently infected (PI) calf. These PI calves are unable to clear the virus in utero, due to an incomplete immune response. However, when infection with BVDV occurs after 150 days of gestation, the fetus clears the transient infection (TI) in utero and is born with antibodies specific to the infecting strain of BVDV. Variations in DNA methylation have been identified in white blood cells (WBC) from TI heifers at birth. It was hypothesized that epigenomic alterations persist into the postnatal period and contribute to previously undocumented pathologies. To study these possible effects, DNA was isolated from the WBCs of 5 TI heifers and 5 control heifers at 4 months of age and subjected to reduced representation bisulfite sequencing (RRBS). Results Differential analysis of the methylome revealed a total of 3,047 differentially methylated CpG sites (DMSs), 1,349 of which were hypermethylated and the other 1,698 were hypomethylated. Genes containing differential methylation were associated with inflammation, reactive oxygen species (ROS) production, and metabolism. Complete blood count (CBC) data identified a higher lymphocyte percentage in TI heifers. When compared in the context of the CD45+ parent population, spectral flow cytometry revealed increased intermediate monocytes, B cells, and CD25+/CD127− T cells, and decreased CD4+/CD8b+ T cells. Comparative analysis revealed differential methylation of CpG sites contained in 205 genes, 5 promoters, and 10 CpG islands at birth that were also present at 4 months of age. Comparison of differential methylation in TI heifers and PI heifers at 4 months of age showed 465 genes, 18 promoters, and 34 CpG islands in common. Conclusion Differential methylation of WBC DNA persists to 4 months of age in TI heifers and is associated with dysregulation of inflammation, metabolism, and growth. Analysis of differential methylation in TI heifers contributes to the understanding of how fetal infection with BVDV induces postnatal detriments related to profit loss.https://doi.org/10.1186/s12864-025-11562-5BVDVEpigeneticsMethylationTransient infectionFetal infection |
| spellingShingle | Jessica N. Kincade Terry E. Engle Marcela Henao-Tamayo Jordan M. Eder Erin M. McDonald Darcy M. Deines Brie M. Wright Dilyara Murtazina Jeanette V. Bishop Thomas R. Hansen Hana Van Campen Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus BMC Genomics BVDV Epigenetics Methylation Transient infection Fetal infection |
| title | Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus |
| title_full | Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus |
| title_fullStr | Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus |
| title_full_unstemmed | Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus |
| title_short | Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus |
| title_sort | postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus |
| topic | BVDV Epigenetics Methylation Transient infection Fetal infection |
| url | https://doi.org/10.1186/s12864-025-11562-5 |
| work_keys_str_mv | AT jessicankincade postnatalepigeneticdifferencesincalvesfollowingtransientfetalinfectionwithbovineviraldiarrheavirus AT terryeengle postnatalepigeneticdifferencesincalvesfollowingtransientfetalinfectionwithbovineviraldiarrheavirus AT marcelahenaotamayo postnatalepigeneticdifferencesincalvesfollowingtransientfetalinfectionwithbovineviraldiarrheavirus AT jordanmeder postnatalepigeneticdifferencesincalvesfollowingtransientfetalinfectionwithbovineviraldiarrheavirus AT erinmmcdonald postnatalepigeneticdifferencesincalvesfollowingtransientfetalinfectionwithbovineviraldiarrheavirus AT darcymdeines postnatalepigeneticdifferencesincalvesfollowingtransientfetalinfectionwithbovineviraldiarrheavirus AT briemwright postnatalepigeneticdifferencesincalvesfollowingtransientfetalinfectionwithbovineviraldiarrheavirus AT dilyaramurtazina postnatalepigeneticdifferencesincalvesfollowingtransientfetalinfectionwithbovineviraldiarrheavirus AT jeanettevbishop postnatalepigeneticdifferencesincalvesfollowingtransientfetalinfectionwithbovineviraldiarrheavirus AT thomasrhansen postnatalepigeneticdifferencesincalvesfollowingtransientfetalinfectionwithbovineviraldiarrheavirus AT hanavancampen postnatalepigeneticdifferencesincalvesfollowingtransientfetalinfectionwithbovineviraldiarrheavirus |