Kincade Jessica N, Engle Terry E, Henao-Tamayo Marcela, Eder Jordan M, McDonald Erin M, Deines Darcy M, Wright Brie M, Murtazina Dilyara, Bishop Jeanette V, Hansen Thomas R, Van Campen Hana
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Department of Animal Sciences, Colorado State University, Fort Collins, CO, USA.
BMC Genomics. 2025 May 2;26(1):441. doi: 10.1186/s12864-025-11562-5.
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).
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.
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.
牛病毒性腹泻病毒（BVDV）是养牛业中最具危害性的瘟病毒。在妊娠125天之前感染垂直传播的BVDV会导致产生持续感染（PI）的犊牛。由于免疫反应不完全，这些PI犊牛在子宫内无法清除病毒。然而，当在妊娠150天之后感染BVDV时，胎儿会在子宫内清除短暂感染（TI），并在出生时带有针对感染性BVDV毒株的抗体。已在出生时TI小母牛的白细胞（WBC）中鉴定出DNA甲基化的变化。据推测，表观基因组改变会持续到出生后，并导致以前未记录的病理情况。为了研究这些可能的影响，在5头TI小母牛和5头对照小母牛4月龄时从其白细胞中分离出DNA，并进行了简化代表性亚硫酸氢盐测序（RRBS）。
甲基化组差异分析共发现3047个差异甲基化的CpG位点（DMS），其中1349个为高甲基化，另外1698个为低甲基化。含有差异甲基化的基因与炎症、活性氧（ROS）产生和代谢有关。全血细胞计数（CBC）数据显示TI小母牛的淋巴细胞百分比更高。在CD45亲本群体的背景下进行比较时，光谱流式细胞术显示中间单核细胞、B细胞和CD25/CD127 T细胞增加，而CD4/CD8b T细胞减少。比较分析显示，出生时205个基因、5个启动子和10个CpG岛中包含的CpG位点的差异甲基化在4月龄时也存在。4月龄时TI小母牛和PI小母牛差异甲基化的比较显示共有465个基因、18个启动子和34个CpG岛。
TI小母牛白细胞DNA的差异甲基化持续到4月龄，并与炎症、代谢和生长的失调有关。对TI小母牛差异甲基化的分析有助于理解胎儿感染BVDV如何引发与利润损失相关的出生后损害。
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