Epigenomic alterations in the postnatal period of calves persistently infected with bovine viral diarrhea virus
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PROVIDER: PRJNA1130515 | ENA |
REPOSITORIES: ENA
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Project description:Bovine Viral Diarrhea Virus (BVDV) is a globally prevalent pathogen that causes severe detriment within the commercial cattle industry. BVDV is a vertically transmissible virus that can cross the placenta, infecting both fetus and dam. Infection occurring before the development of the fetal adaptive immune response, prior to approximately 125 days of gestation, results in a persistently infected (PI) calf. The PI calf is unable to produce BVDV specific antibodies, is immunotolerant, and sheds virus consistently. PI fetuses display alterations of the methylome and proteome at day 245 of gestation corresponding to pathologies of the immune system, bone, brain, and heart. It was hypothesized that epigenetic alterations observed in the prenatal period are a remnant of fetal programming due to fetal BVDV infection and persist into the postnatal period. To test this hypothesis, white blood cells were isolated from whole blood collected from 5 PI and 5 control heifers at 4 months of age and subjected to reduced representation bisulfite sequencing. Analysis of the methylome at 4 months of age indicated that 5,349 (64%) of the identified differentially methylated CpG sites (DMSs) were hypomethylated and 3,018 (36%) of DMSs were hypermethylated. Genes in which DMSs were identified were associated with the immune system, hematopoiesis, and the cardiac system. Complete blood count and flow cytometry data corroborate abnormalities of the immune response. Data presented here introduces a new perspective on the predisposition of PI cattle to fatal secondary infections.
2025-05-30 | GSE271244 | GEO
Project description:Bovine Viral Diarrhea Virus (BVDV) is the most detrimental flavivirus 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 BVDV specific antibodies. Variations in DNA methylation have been identified in white blood cells (WBC) of TI heifers at birth. It was hypothesized that epigenomic alterations persist into the postnatal period and lead 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 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.
2025-03-28 | GSE288374 | GEO
Project description:Dampness heat diarrhea (DHD) is the leading cause in calves with diarrhea in traditional Chinese medicine (TCM). However, the methods for detecting DHD diarrhea remain subjective or infective. To address this issue, the calves with dampness heat diarrhea were collected and the plasma proteomic was analyzed using data-independent acquisition (DIA)-mass spectrometry- based proteomics. The analysis revealed a total of 52 differentially expressed proteins that were uniquely altered in the DHD calves’ plasma, compared to the control. Bioinformatics analysis showed that these altered proteins were involved in a wide range of biological processes, such as intestinal immune network for IgA production, purine metabolism and PI3K signaling pathway, which implying their potential roles in DHD.
2022-10-14 | PXD027099 | Pride
Project description:Postnatal epigenetic differences in calves following transient fetal infection with bovine viral diarrhea virus
| PRJNA1217047 | ENA
Project description:Fecal microbiota in dairy calves with diarrhea
| PRJNA407697 | ENA
Project description:Dampness heat diarrhea (DHD) is the most common type of diarrhea in calves according to the Traditional Chinese veterinary medicine (TCVM) and its complex etiology bring great challenges to the treatment of this disease. Huangbai jianpi decoction (HBJP) is efficacy to treat DHD in calves. The therapeutic mechanism of HBJP is urgently required to be applied this decoction to the precise treatment of this syndrome in the clinic. We herein aimed to explore the mechanism of HBJP in DHD by using multi-omic analysis from DHD calves in Northwest China region. Proteomic results showed that some protein, including coagulation factor XIII B chain precursor (F13 B), alpha-1-acid glycoprotein precursor (ORM1) and polymeric immunoglobulin receptor (PIGR), had significant changes after treatment with HBJP. Metabolomics data demonstrated that the plasma of DHD calves were associated with high abundance of choline and pirbuterol, while after treated by HBJP the plasma was abundant in glycocholic acid and taurocholic acid. Bacterial gene sequence analysis showed that the feces of DHD calves had the highest abundance of Escherichia-Shigella, while after treated by HBJP the feces were more enriched in Megasphaera, Prevotella_2 and Bifidobacterium. Our study demonstrated that plasma proteins and metabolites, and gut microbiota were significantly different between before and after treated by HBJP in calves, and provided the theoretical basis for elucidating the mechanism of HBJP in the treatment of DHD.
2023-09-11 | PXD045280 |
Project description:In cattle, two of the most common technologies for embryo production are “in vivo”, after multiple ovulation and embryo transfer (MOET), or “in vitro” (IVP). IVP can sometimes impact fetal growth, resulting in large offspring, although most IVP calves are born apparently healthy. However, gene regulation changes in the organs involved in the developmental process in phenotypically normal postnatal calves are unknown and could indicate physiological programming. The objective was to compare the epigenomic and transcriptomic modifications in the liver, muscle, and organs of the hypothalamus-pituitary-gonadal and adrenal (HPGA) axes between IVP and MOET male calves of three months of age. Pregnancies were monitored until delivery. Male calves were maintained in similar conditions during the postnatal period until euthanasia at around 100 days of age. There were no differences regarding body weight at birth and growth rate among the animals in both groups at this age.
2023-01-17 | GSE223098 | GEO
Project description:The impact of late-term fetal bovine viral diarrhea virus (BVDV) transient infections (TI) on fetal growth and methylome was examined by inoculating pregnant heifers with a noncytopathic (ncp) type 2 BVDV suspended in media or media alone (sham-inoculated controls) on day 175 of gestation to generate TI (n=11) and control heifer calves (n=12). Blood samples were collected at birth. White blood cells (WBC) were separated for DNA extraction. Fetal infection in calves was confirmed by positive virus serum 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. DNA methyl seq analysis of WBC DNA demonstrated 2,349 differentially methylated cytosines (p≤0.05) including 1,277 hypomethylated cytosines, 1.072 hypermethylated cytosines, 84 differentially methylated regions based on CpGs in promoters and 89 DMRs based on CpGs in exons of TI WBC DNA compared to controls. Fetal BVDV infection during late gestation resulted in epigenomic modifications predicted to affect fetal and organ development pathways suggesting potential consequences for postnatal growth and health of TI cattle.
2024-05-29 | GSE255721 | GEO
Project description:Bovine Viral Diarrhea Virus (BVDV) is an endemic virus of North American cattle populations with significant economic and animal health impacts. While BVDV infection has a myriad of clinical manifestations, a unique and problematic outcome is the establishment of a persistently infected (PI) animal following in-utero viral infection. While it is well established that PI animals serve as a constant reservoir of BVDV, the mechanism for the maintained infection remains unknown despite multiple theories. The purpose of this study was to use transcriptome analysis to further define long term immune status of adult PI cattle and offer insight into the potential mechanistic establishment of persistent BVDV infection, in utero. Peripheral blood mononuclear cells were collected from PI beef cattle (N=6) and uninfected controls (N=6) for targeted RNAseq analysis conducted using 54 genes of interest and followed by pathway enrichment analysis. Analysis revealed 29 differentially expressed genes (FDR < 0.05, fold change > 2) representing 14 significant KEGG pathways between PI and control animals (FDR < 0.05). Transcriptome changes indicate chronic upregulation of interferon gamma (IFNG) with unexpected expression of related genes, suggesting a maintained stimulation of the PI immune system resulting in virus-mediated dysregulation of immune function.
2024-12-10 | GSE278855 | GEO
Project description:Targeted Transcriptome Analysis of Beef Cattle Persistently Infected with Bovine Viral Diarrhea Virus
| PRJNA1169059 | ENA