短暂性胎儿感染牛病毒性腹泻病毒导致的白细胞 DNA 的表观遗传修饰。

Epigenetic Modifications of White Blood Cell DNA Caused by Transient Fetal Infection with Bovine Viral Diarrhea Virus.

机构信息

Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.

Department of Animal Science, Colorado State University, Fort Collins, CO 80523, USA.

出版信息

Viruses. 2024 May 1;16(5):721. doi: 10.3390/v16050721.

DOI:10.3390/v16050721

PMID:38793603

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11125956/

Abstract

Bovine viral diarrhea virus (BVDV) infections cause USD 1.5-2 billion in losses annually. Maternal BVDV after 150 days of gestation causes transient fetal infection (TI) in which the fetal immune response clears the virus. The impact of fetal TI BVDV infections on postnatal growth and white blood cell (WBC) methylome as an index of epigenetic modifications was examined by inoculating pregnant heifers with noncytopathic type 2 BVDV or media (sham-inoculated controls) on Day 175 of gestation to generate TI ( = 11) and control heifer calves ( = 12). Fetal infection in TI calves was confirmed by virus-neutralizing antibody titers at birth and control calves were seronegative. Both control and TI calves were negative for BVDV RNA in WBCs by RT-PCR. The mean weight of the TI calves was less than that of the controls ( < 0.05). DNA methyl seq analysis of WBC DNA demonstrated 2349 differentially methylated cytosines ( ≤ 0.05) including 1277 hypomethylated cytosines, 1072 hypermethylated cytosines, 84 differentially methylated regions based on CpGs in promoters, and 89 DMRs in islands of TI WBC DNA compared to controls. Fetal BVDV infection during late gestation resulted in epigenomic modifications predicted to affect fetal development and immune pathways, suggesting potential consequences for postnatal growth and health of TI cattle.

摘要

牛病毒性腹泻病毒（BVDV）感染每年造成 15 亿至 20 亿美元的损失。妊娠 150 天后的母体 BVDV 会导致胎儿一过性感染（TI），在此期间，胎儿的免疫反应会清除病毒。本研究通过在妊娠 175 日龄时给妊娠小母牛接种非致细胞病变型 2 型 BVDV 或培养基（假接种对照），来检测胎儿 TI BVDV 感染对产后生长和白细胞（WBC）甲基组（作为表观遗传修饰的指标）的影响，共获得 11 头 TI 小牛和 12 头对照小母牛。TI 小牛在出生时的病毒中和抗体滴度证实了胎儿感染，而对照小牛血清学均为阴性。RT-PCR 检测结果显示，WBC 中 TI 小牛和对照小牛的 BVDV RNA 均为阴性。TI 小牛的平均体重小于对照小牛（<0.05）。WBC DNA 的 DNA 甲基化测序分析表明，有 2349 个差异甲基化胞嘧啶（≤0.05），包括 1277 个低甲基化胞嘧啶、1072 个高甲基化胞嘧啶、84 个基于启动子 CpG 的差异甲基化区域，以及 TI WBC DNA 中 89 个 DMRs。妊娠晚期胎儿 BVDV 感染导致了表观基因组修饰，这些修饰可能会影响胎儿的发育和免疫途径，提示 TI 牛的产后生长和健康可能存在潜在影响。