scholarly journals Th17 Cell Differentiation Induced by Cytopathogenic Biotype BVDV-2 in Bovine PBLCs

2021 ◽  
Author(s):  
Yanping Li ◽  
Tingli Liu ◽  
Guoliang Chen ◽  
Liqun Wang ◽  
Aimin Guo ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Signaling Pathway ◽  
Th17 Cell ◽  
Bovine Viral Diarrhea ◽  
Control Group ◽  
Sequencing Analysis ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Th17 Cell Differentiation ◽  
Transcriptomic Sequencing

Abstract Background: Bovine viral diarrhea virus (BVDV) is a major pathogen that causes bovine viral diarrhea/mucosal disease (BVD-MD), which has become a global infectious disease due to its wide spread and the lack of effective treatment. The process of BVDV infection is complex. Once infected, host immune cells are activated and modulated. As a major immune cell, peripheral blood lymphocyte cells (PBLCs) are the primary target of BVDV. In order to further understand the mechanism of BVDV- host interaction, the expression profiles of host lymphocytes mRNAs associated with BVDV infection were investigated by transcriptomic sequencing analysis. Results: The transcriptomic sequencing analysis was performed on bovine PBLCs infected with CP BVDV-2 GS2018 after 12 h of infection. Gene expression profiling demonstrated that 1,052 genes were differentially expressed in GS2018 infected PBLCs compared with the control group. Of these genes, 485 genes were up-regulated and 567 were down-regulated. 19 differential expressed genes (DEGs) were selected for validation using quantitative real-time PCR and the results were consistent with the results of RNA-Seq. Gene ontology enrichment and KEGG pathway analysis showed that 1052 DEGs were significantly enriched in 16 pathways, including cytokine-cytokine receptor interaction, IL17 signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway and TNF signaling pathway. PPI network analysis showed that IL17A, IFN-γ and TNF-α interacted with various proteins and may play crucial roles in BVDV-2 infection. Of note, we confirmed that GS2018 induced Th17 cell differentiation in PBLCs and persistently increased the expression levels of IL17A. In turn, the replication of GS2018 was inhibited by IL17A. Conclusion: In this study, the transcription changes of DEGs related to host immune responses in bovine PBLCs were caused by CP BVDV-2 infection. In particular, the effector molecules IL17A of Th17 cells were significantly up-regulated, which inhibited viral replication. These results will contribute to exploration and further understanding of the host immune response mechanism and interaction between host and BVDV-2.

scholarly journals Th17 cell differentiation induced by cytopathogenic biotype BVDV-2 in bovine PBLCs

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanping Li ◽  
Tingli Liu ◽  
Guoliang Chen ◽  
Liqun Wang ◽  
Aimin Guo ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Th17 Cell ◽  
Receptor Interaction ◽  
Bovine Viral Diarrhea ◽  
Control Group ◽  
Sequencing Analysis ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Th17 Cell Differentiation ◽  
Transcriptomic Sequencing

Abstract Background Bovine viral diarrhea virus (BVDV) is a major pathogen that causes bovine viral diarrhea/mucosal disease (BVD-MD), which has become a global infectious disease due to its wide spread and the lack of effective treatment. The process of BVDV infection is complex. Once infected, host immune cells are activated and modulated. As a major immune cell, peripheral blood lymphocyte cells (PBLCs) are the primary target of BVDV. In order to further understand the mechanism of BVDV- host interaction, the expression profiles of host lymphocytes mRNAs associated with BVDV infection were investigated by transcriptomic sequencing analysis. Results The transcriptomic sequencing analysis was performed on bovine PBLCs infected with CP BVDV-2 GS2018 after 12 h of infection. Gene expression profiling demonstrated that 1052 genes were differentially expressed in GS2018 infected PBLCs compared with the control group. Of these genes, 485 genes were up-regulated and 567 were down-regulated. The 19 differential expressed genes (DEGs) were selected for validation using quantitative real-time PCR and the results were consistent with the results of RNA-Seq. Gene ontology enrichment and KEGG pathway analysis showed that 1052 DEGs were significantly enriched in 16 pathways, including cytokine-cytokine receptor interaction, IL17, PI3K-Akt, MAPK and TNF signaling pathway. PPI network analysis showed that IL17A, IFN-γ and TNF-α interacted with various proteins and may play crucial roles in BVDV-2 infection. Of note, we confirmed that GS2018 induced Th17 cell differentiation in PBLCs and persistently increased the expression levels of IL17A. In turn, the replication of GS2018 was inhibited by IL17A. Conclusion In this study, the transcription changes of DEGs related to host immune responses in bovine PBLCs were caused by CP BVDV-2 infection. In particular, the effector molecules IL17A of Th17 cells were significantly up-regulated, which inhibited viral replication. These results will contribute to exploration and further understanding of the host immune response mechanism and interaction between host and BVDV-2.

scholarly journals Isolation and Genetic Analysis of Bovine Viral Diarrhea Virus from Infected Cattle in Indiana

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Roman M. Pogranichniy ◽  
Megan E. Schnur ◽  
Eran A. Raizman ◽  
Duane A. Murphy ◽  
Maria Negron ◽  
...  
Keyword(s):  
Bovine Viral Diarrhea Virus ◽  
Clinical Signs ◽  
Bovine Viral Diarrhea ◽  
Sequencing Analysis ◽  
Diagnostic Laboratory ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Mucosal Disease ◽  
Pcr Product ◽  
Viral Diarrhea Virus

Species and biotype distribution was determined in 44 bovine viral diarrhea virus- (BVDV-) positive samples submitted to the Animal Disease Diagnostic Laboratory (ADDL) in Indiana during 2006–2008. BVDV RNA was detected in the 5′-untranslated region and Nproregion using reverse transcriptase PCR followed by sequencing analysis of the PCR product. Additionally, cases were classified into one of six categories according to history and/or lesions: acute symptomatic, hemorrhagic, respiratory distress, reproductive, persistent infection (PI), and mucosal disease (MD). Of 44 BVDV-positive samples, 33 were noncytopathic (ncp), 10 were cytopathic (cp), and one presented both ncp and cp biotypes. Sequencing analysis demonstrated that all samples belonged to BVDV-1a, BVDV-1b, or BVDV-2. The most common isolate was ncp BVDV-1b, (44%) followed by ncp BVDV-2a (24%). Among the six categories, respiratory clinical signs were the most common (36%) followed by PI (25%) and MD (16%).

scholarly journals ITRAQ-based quantitative proteomics reveals the proteome profiles of MDBK cells infected with bovine viral diarrhea virus

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yaxin Li ◽  
Tao Guo ◽  
Xiaokui Wang ◽  
Wei Ni ◽  
Ruirui Hu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bovine Viral Diarrhea Virus ◽  
Quantitative Proteomics ◽  
Differentially Expressed ◽  
Bovine Viral Diarrhea ◽  
Metabolic Processes ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Mdbk Cells ◽  
Viral Diarrhea Virus

Abstract Background Bovine viral diarrhea (BVD) which is caused by Bovine viral diarrhea virus (BVDV), is an acute, contagious disease. In spite of the use of vaccines and elimination projects, BVDV still causes severe economic losses to the cattle industry for the past few years. The current study presents a preliminary analysis of the pathogenic mechanisms from the perspective of protein expression levels in infected host cells at different points in time to elucidate the infection process associated with BVDV. Methods We used the isobaric tags for relative and absolute quantitation (iTRAQ) technology coupled with liquid chromatography-tandem mass spectrometric (LC–MS/MS) approach for a quantitative proteomics comparison of BVDV NADL-infected MDBK cells and non-infected cells. The functions of the proteins were deduced by functional annotation and their involvement in metabolic processes explored by KEGG pathway analysis to identify their interactions. Results There were 357 (47.6% downregulated, 52.4% upregulated infected vs. control), 101 (52.5% downregulated, 47.5% upregulated infected vs. control), and 66 (21.2% downregulated, 78.8% upregulated infected vs. control) proteins were differentially expressed (fold change > 1.5 or < 0.67) in the BVDV NADL-infected MDBK cells at 12, 24, and 48 h after infection. GO analysis showed that the differentially expressed proteins (DEPs) are mainly involved in metabolic processes, biological regulation and localization. KEGG enrichment analysis showed that some signaling pathways that involved in the regulation of BVDV NADL-infection and host resistance are significantly (P < 0.05) enriched at different stages of the BVDV NADL-infection, such as Endocytosis signaling pathway, FoxO signaling pathway, Homologous recombination signaling pathway and Lysosome pathway. Conclusions These results revealed that the DEPs in BVDV NADL-infected MDBK cells have a wide range of regulatory effects; in addition, they provide a lot of resources for the study of host cell proteomics after BVDV infection.

scholarly journals ITRAQ-Based quantitative proteomics reveals the proteome profiles of MDBK cells infected with bovine viral diarrhea virus

2020 ◽  
Author(s):  
Yaxin Li ◽  
Tao Guo ◽  
Xiaokui Wang ◽  
Wei Ni ◽  
Ruirui Hu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bovine Viral Diarrhea Virus ◽  
Quantitative Proteomics ◽  
Differentially Expressed ◽  
Bovine Viral Diarrhea ◽  
Metabolic Processes ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Mdbk Cells ◽  
Viral Diarrhea Virus

Abstract Background Bovine viral diarrhea (BVD) which is caused by Bovine viral diarrhea virus (BVDV), is an acute, contagious disease. In spite of the use of vaccines and elimination projects, BVDV is still found to cause severe financial losses to the cattle industry for the past years. The current study presents a preliminary analysis of the pathogenic mechanisms from the perspective of protein expression levels in infected host cells at different points in time to elucidate the infection process associated with BVDV. Methods We used the isobaric tags for relative and absolute quantitation (iTRAQ) technology coupled with liquid chromatography-tandem mass spectrometric (LC-MS/MS) approach for a quantitative proteomics comparison of BVDV NADL-infected MDBK cells and non-infected cells. The functions of the proteins were deduced by functional annotation and their involvement in metabolic processes explored by KEGG pathway analysis to identify their interactions. Results There were 357 (47.6% downregulated, 52.4% upregulated infected vs. control), 101 (52.5% downregulated, 47.5% upregulated infected vs. control), and 66 (21.2% downregulated, 78.8% upregulated infected vs. control) proteins were differentially expressed (fold change > 1.5 or < 0.67) in the BVDV NADL-infected MDBK cells at 12, 24, and 48 h after infection. GO analysis showed that the differentially expressed proteins (DEPs) are mainly involved in metabolic processes, biological regulation and localization. KEGG enrichment analysis showed that some signaling pathways that involved in the regulation of BVDV NADL-infection and host resistance are significantly (P < 0.05) enriched at different stages of the BVDV NADL-infection, such as Endocytosis signaling pathway, FoxO signaling pathway, Homologous recombination signaling pathway and Lysosome pathway. Conclusions These results revealed that the DEPs in BVDV NADL-infected MDBK cells have a wide range of regulatory effects; in addition, they provide a lot of resources for the study of host cell proteomics after BVDV infection.

scholarly journals Melatonin as Immune Potentiator for Enhancing Subunit Vaccine Efficacy against Bovine Viral Diarrhea Virus

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1039
Author(s):  
Yi-Xuan Wang ◽  
Guang-Hui Yang ◽  
Lin-Lin Zhang ◽  
Jing Wang ◽  
Jiu-Feng Wang
Keyword(s):  
Signaling Pathway ◽  
Bovine Viral Diarrhea Virus ◽  
Economic Losses ◽  
Bovine Viral Diarrhea ◽  
Mrna Levels ◽  
Diarrhea Virus ◽  
Viral Diarrhea ◽  
Viral Diarrhea Virus

Bovine viral diarrhea virus (BVDV) is a pathogen associated with substantial economic losses in the dairy cattle industry. Currently, there are no effective vaccines against BVDV. Melatonin (MT) has been shown to have anti-inflammatory and anti-viral properties, and the use of MF59 in vaccines significantly enhances vaccine efficiency. Here, MT and MF59 were added into the Erns-LTB vaccine. Subsequently, their inhibitory activity on the NF-κB signaling pathway in Mardin-Darby Bovine Kidney cells and the hippocampus was assessed using western blot and quantitative reverse transcription PCR. The findings revealed that MT in the Erns-LTB vaccine decreases the phosphorylation of p65 proteins caused by BVDV infection. In addition, MT decreased the mRNA levels of IL-1β and IL-6 in vitro, but increased the production of IFN-α, IFN-β, Mx1 in vitro, brain-derived neurotrophic factor, cyclic amp response element-binding protein, and the stem cell factor in vivo. Furthermore, treatment with Erns-LTB + MF59 + MT stimulated the production of T lymphocytes, alleviated pathological damage, decreased expressions of BVDV antigen, and tight junction proteins in mice. These findings imply that MT has potential for use in the Erns-LTB vaccine to inhibit BVDV infection and regulate the immune responses of T-cells by inhibiting the NF-κB signaling pathway.

scholarly journals Integrative blood-derived epigenetic and transcriptomic analysis reveals the potential regulatory role of DNA methylation in ankylosing spondylitis

2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Min Xiao ◽  
Xuqi Zheng ◽  
Xiaomin Li ◽  
Xinyu Wu ◽  
Yefei Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Differentiation ◽  
Ankylosing Spondylitis ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Th17 Cell ◽  
Tcr Signaling ◽  
Th17 Cell Differentiation ◽  
Independent Cohort

Abstract Background The currently known risk loci could explain a small proportion of the heritability of ankylosing spondylitis (AS). Epigenetics might account for the missing heritability. We aimed to seek more novel AS-associated DNA methylation alterations and delineate the regulatory effect of DNA methylation and gene expression with integrated analysis of methylome and transcriptome. Methods Epigenome-wide DNA methylation and mRNA expression were profiled in peripheral blood mononuclear cells (PBMCs) from 45 individuals (AS: health controls (HCs) = 30:15) with high-throughput array. The methylome was validated in an independent cohort (AS: HCs = 12:12). Pearson correlation analysis and causal inference tests (CIT) were conducted to determine potentially causative regulatory effects of methylation on mRNA expression. Results A total of 4794 differentially methylated positions (DMPs) were identified associated with AS, 2526 DMPs of which were validated in an independent cohort. Both cohorts highlighted T cell receptor (TCR) signaling and Th17 differentiation pathways. Besides, AS patients manifested increased DNA methylation variability. The methylation levels of 158 DMPs were correlated with the mRNA expression levels of 112 genes, which formed interconnected network concentrated on Th17 cell differentiation and TCR signaling pathway (LCK, FYN, CD3G, TCF7, ZAP70, CXCL12, and PLCG1). We also identified several cis-acting DNA methylation and gene expression changes associated with AS risk, which might regulate the cellular mechanisms underlying AS. Conclusions Our studies outlined the landscapes of epi-signatures of AS and several methylation-gene expression-AS regulatory axis and highlighted the Th17 cell differentiation and TCR signaling pathway, which might provide innovative molecular targets for therapeutic interventions for AS.

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