Marek's Disease Virus Infection Induces Differential Chromatin Marks and Tissue-specific effects in inbred chicken lines
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ABSTRACT:
ORGANISM(S): Gallus gallus
SUBMITTER: Apratim Mitra
PROVIDER: E-GEOD-33541 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Background: Marek’s disease (MD) is a highly contagious, lymphomatous disease of chickens induced by a herpesvirus, Marek’s disease virus (MDV) that is the cause of major annual losses to the poultry industry. MD pathogenesis involves multiple stages including an early cytolytic phase and latency, and transitions between these stages are governed by several host and environmental factors. The success of vaccination strategies has led to the increased virulence of MDV and selective breeding of naturally resistant chickens is seen as a viable alternative. While multiple gene expression studies have been performed in resistant and susceptible populations, little is known about the epigenetic effects of infection. Results: In this study, we investigated temporal chromatin signatures induced by MDV by analyzing early cytolytic and latent phases of infection in the bursa of Fabricius of MD-resistant and –susceptible birds. Major global variations in chromatin marks were observed at different stages of MD in the two lines. Differential H3K27me3 marks were associated with immune-related pathways, such as MAP kinase signaling, focal adhesion and neuroactive ligand receptor interaction, and suggested varying degrees of silencing in response to infection. Immune-related microRNAs, e.g. gga-miR-155 and gga-miR-10b, bore chromatin signatures, which suggested their contribution to MD-susceptibility. Finally, several members of the focal adhesion pathway, e.g. THBS4 and ITGA1, showed marked concordance between gene expression and chromatin marks indicating putative epigenetic regulation in response to MDV infection. Conclusions: Our comprehensive analysis of chromatin signatures, therefore, revealed further clues about the epigenetic effects of MDV infection although further studies are necessary to elucidate the functional implications of the observed variations in histone modifications. Total of 32 samples analyzed; 2 histone modifications - H3K4me3 and H3K27me3 x 2 chicken lines with varying resistance to MD - L63 and L72 x 2 time-points of disease progression - 5 and 10 days post infection x 2 conditions - infected and control x 2 biological replicates
2015-04-17 | E-GEOD-65961 | biostudies-arrayexpress
Project description:To investigate specific miRNA expression profiles of Marek's disease virus (MDV)-infected samples, we performed deep sequencing for miRNAs in four small RNA libraries, including MDV-infected tumorous spleen, MD lymphoma from liver, and non-infected spleen and lymphocytes from controls. A total of 7.76x106, 6.36x106, 6.36x106, and 7.60x106 counts were obtained in four libraries, respectively. The sequences were blasted with chicken and MDV genomes and miRBase 16.0 to identify known and novel miRNAs. In total, 187 and 16 known mature miRNAs were identified in the chicken and MDV, respectively. Deep sequencing detected 942 novel chicken miRNA candidates, of which 646 were in tumorous spleen. These results indicate that MDV infection induced new host miRNA candidates and increased diversity of miRNAs. Of 942 miRNA candidates, 276 of 533 were verified by customized microarray, and 17 of them were further confirmed by qPCR. Four samples examined: MDV-infected tumorous spleen, MD lymphoma from liver, Non-infected spleen, Non-infected lymphocytes
2013-12-30 | E-GEOD-31349 | biostudies-arrayexpress
Project description:Marek’s disease (MD) is a viral neoplastic disease in chickens caused by the MD virus (MDV). Successful vaccination strategies against MD have resulted in a progressive increase in the virulence of MDV and therefore, the understanding of genetic resistance to MD is considered crucial to the long-term control of the disease. Here we examine whether MDV infection induces changes in the epigenetic status of genes and whether this response is dependent on the host genotype. We generated genome-wide histone 3 lysine 4 (H3K4) and histone 3 lysine 27 (H3K27) trimethylation maps in thymus tissues from chicken lines with varying resistance to MD. Differential chromatin marks were observed on several genes previously implicated in MD such as MX1, MMP2 and CTLA-4 and also on novel genes such as EAF2, IGF2BP1 and GAL. We also detected bivalent domains on transcriptional regulators such as BCL6, CITED2 and EGR1 that have particular functions in immune response. Moreover, novel putative roles for GAL and CITED2 in the mechanism of MD progression were uncovered. We also found tissue-specific effects of MDV infection with certain genes exhibiting differential marks only in spleen. Our results suggest widespread epigenetic changes are induced by MDV infection extent of which is determined by the level of MD resistance of the host.
2013-01-01 | GSE33541 | GEO
Project description:Marek's disease virus (MDV) is a highly contagious oncogenic herpes virus. Classed as an alpha herpes virus due to its DNA sequence and genome organization, its biological properties are more similar to those of gamma herpes viruses. MDV causes an initial cytolytic infection in B lymphocytes (3-6dpi) followed by infection of CD4+ T cells (at around 7dpi) where the virus becomes latent (for around two weeks) and then goes on to produce lymphoid tumours in the skin, nerves and internal organs. Early symptoms in susceptible birds include lameness, paralysis, loss of appetite, depression, blindness and immuno-suppression. The route of infection is usually respiratory and the disease is highly contagious, being spread by infective feather-follicle dander. Although birds may survive MDV infection, the resultant immuno-suppression leaves the birds highly susceptible to other infections. MDV infection can thus be associated with high mortality rates and, in turn, large economic losses throughout the worldï¾Âs poultry industry. Three-week-old chicks were inoculated with virus (RB1B) via an intra-gastric route and tissue samples were collected at 2, 3 and 4 days post-inoculation. Spleen and thymus tissue were examined from control and infected birds at 2, 3 and 4 days post-infection in birds known to be either susceptible or resistant to the virus. As well as understanding the host immune response to MDV, we are interested in identifying genes involved in disease resistance and so we have analysed the gene expression profiles at these times, when the innate immune response is active. We assume that genes underlying resistance will be involved at this early stage of the host immune response.
2010-12-31 | E-TABM-721 | biostudies-arrayexpress
Project description:Chicken MarekM-bM-^@M-^Ys disease (MD) is a unique naturally occurring model for human herpesvirus-induced lymphomas that over-express the M-bM-^@M-^\HodgkinM-bM-^@M-^Ys disease antigenM-bM-^@M-^] (TNFRSF-8; CD30) on the lymphomaM-bM-^@M-^Ys neoplastically-transformed cells. We used transcriptomics, proteomics, computational systems biology and reductionist molecular biology to identify the differences between the CD30(hi) lymphoma cells and the non-transformed CD30(lo) MD lymphoma cells. We propose specific mechanisms of neoplastic transformation, genetic resistance to lymphomagenesis and impact of lymphoma microenvironment on CD30(hi) cell development. We demonstrate that: a) in situ, CD30(lo) cells are pre-neoplastic and we identify the proteome involved in transformation as well as potential mechanisms that may be controlled by MDV oncogene Meq; b) MD herpesvirus, (via its Meq oncogene) can drive a feed forward loop that induces CD30 transcription and overexpression, increased CD30 signaling, which then activates NFM-NM-:B and, in turn, increases Meq transcription; c) Meq transcriptional repression or activation from the CD30 promoter generally correlates with a polymorphism in the CD30 promoter between MD-resistant and -susceptible chicken genotypes and so a herpesvirus has evolved to utilize NFM-NM-:B as a direct transcriptional activator for its oncogene. A dual color, balanced design was carried on eight sorted lymphoma cells from white leghorn chickens infected with MDV GA/22 strain. Each of two sample types, CD30(hi) and CD30(lo) cells, includes four biological replicates for total RNA extraction and labeling. A Dye swap was used in four biological repeats of CD30(hi) to CD30(lo) cells comparison. Background subtracted signal intensities were collected from 4 arrays and normalized for data analysis.
2012-03-15 | E-GEOD-28034 | biostudies-arrayexpress
Project description:Marek’s disease (MD) is an economically significant disease in chickens caused by the highly oncogenic Marek’s disease virus (MDV). Understanding the genes and biological pathways that confer MD genetic resistance should lead towards the development of more disease resistant commercial poultry flocks or improved MD vaccines. MDV Meq, a bZIP transcription factor, is largely attributed for viral oncogenicity though only a few host target genes have been described, which has impeded our understanding of MDV-induced tumorigenesis. Given the importance of Meq in MDV-induced pathogenesis, we explored the role of Meq in genetic resistance to MDV. Using global transcriptome analysis to compare the host response between birds challenge with either wild type MDV or a recombinant lacking Meq, we identified a number of specific genes and pathways associated with either MD resistance. Integrating prior information from ChIP-seq, microarray analysis, and SNPs exhibiting allele-specific expression (ASE) in response to MDV infection from two inbred layer lines that differ greatly in MD genetic resistance, we were able to provide a evidence for 35 genes that SNPs within transcription factor binding sites can affect transcription factor binding and gene expression in an allele-specific manner.
2016-07-01 | GSE48453 | GEO
Project description:Marekâs disease (MD) is an economically significant disease in chickens caused by the highly oncogenic Marekâs disease virus (MDV). Understanding the genes and biological pathways that confer MD genetic resistance should lead towards the development of more disease resistant commercial poultry flocks or improved MD vaccines. MDV Meq, a bZIP transcription factor, is largely attributed for viral oncogenicity though only a few host target genes have been described, which has impeded our understanding of MDV-induced tumorigenesis. Given the importance of Meq in MDV-induced pathogenesis, we explored the role of Meq in genetic resistance to MDV. Using global transcriptome analysis to compare the host response between birds challenge with either wild type MDV or a recombinant lacking Meq, we identified a number of specific genes and pathways associated with either MD resistance. Integrating prior information from ChIP-seq, microarray analysis, and SNPs exhibiting allele-specific expression (ASE) in response to MDV infection from two inbred layer lines that differ greatly in MD genetic resistance, we were able to provide a evidence for 35 genes that SNPs within transcription factor binding sites can affect transcription factor binding and gene expression in an allele-specific manner. Transcript profiling of CEF's (a chicken embryo fibroblast cell line) from MD susceptible and resistant lines using Affymetrix chicken GeneChips
2016-07-01 | E-GEOD-48453 | biostudies-arrayexpress
Project description:To investigate gene expression profiles in susceptible spleens (SS) and resistant spleens (RS) from MDV-infected chickens and non-infected spleens (NS) from controls. Twelve spleens were chosen from three groups (four samples per group) to be used in chicken genome microarray to examine differential gene expression. In total, there were 4317 and 2593 differentially expressed (DE) genes in SS vs. NS and in SS vs. RS, respectively. However, no DE genes were found in RS vs. NS. The expression of twenty-four genes was verified by qPCR. In this study, we found weak, but detectable host immune response still existed in the late neoplastic transformation phase of MDV infection. Toll-like receptor pathway was affected in susceptible spleens compared to non-infected and resistant spleens. IL10 seemed to be exploited by virus to facilitate tumorigenesis. The expression of many members in insulin growth factor system was altered. IGFBP4 and IGFBP7 might be associated with MD lymphoma transformation. The expression profiles in resistant spleens were similar to those in non-infected spleens, which indicated most genes returned to baseline expression levels. Although latent MDV infection persists in resistant chicken for the whole life, it wonM-bM-^@M-^Yt interfere with normal function of genes. Four susceptible spleens with tumors were obtained at 46-55 d.p.i., four resistant spleens were removed from survivors at 55-56 d.p.i. from MDV infected chickens, and four non-infected spleens were from controls at 40-56 d.p.i. Twelve one-color microarrays were utilized to detect differential gene expression among three groups.
2012-05-31 | E-GEOD-29805 | biostudies-arrayexpress
Project description:The generation of mitochondrial-derived vesicles (MDVs) is implicated in a plethora of vital cell functions, from mitochondrial quality control to peroxisomal biogenesis. The discovery of distinct subtypes of MDVs has revealed the selective inclusion of mitochondrial cargo in response to varying stimuli. However, the true scope and variety of MDVs is currently unclear, and unbiased approaches have yet to be used to understand their biology. Furthermore, as mitochondrial dysfunction has been implicated in many neurodegenerative diseases, it is essential to understand MDV pathways in the nervous system. To address this, we sought to identify the cargo in brain MDVs. We used an in vitro budding assay and proteomic approach to identify proteins selectively enriched in MDVs. 72 proteins were identified as MDV enriched, of which 31% were OXPHOS proteins. Interestingly, the OXPHOS proteins localized to specific modules of the respiratory complexes, hinting at the inclusion of sub-assemblies in MDVs. Small TIM chaperones were also highly enriched in MDVs, linking mitochondrial chaperone-mediated protein transport to MDV formation. As the two Parkinson’s disease genes PINK1 and Parkin have been previously implicated in MDV biogenesis in response to oxidative stress, we compared the MDV proteomes from the brains of wild-type mice with those of PINK1-/- and Parkin-/- mice. No significant difference was found, suggesting that PINK1- and Parkin-dependent MDVs make up a small proportion of all MDVs in the brain. Our findings demonstrate a previously uncovered landscape of MDV complexity and provide a foundation from which to discover further novel MDV functions.
2020-09-07 | PXD020197 | Pride
Project description:Purpose: Marek's disease virus (MDV) is an oncogenic herpesvirus that can induce T-cell lymphoma. Long noncoding RNA (lncRNA) strongly associated with various cancers and many other diseases. In chickens, lncRNAs have not been comprehensively identified. Here, we profiled mRNA and lncRNA repertoires in three groups of spleens from MDV-infected and non-infected chickens, including seven tumorous spleens (TS) from MDV-infected chickens, five spleens from the survivors (SS) without any lesion after MDV infection, and five noninfected spleens (NS) from chickens, to explore the underlying mechanism of host resistance to Marek's disease (MD). Results: By using precise lncRNA identification pipeline, we identified 1315 putative lncRNAs and 1166 known lncRNAs in spleen tissue. Genomic features of putative lncRNAs were characterized. Differentially expressed mRNAs, putative lncRNAs and known lncRNAs were profiled. Some previously reported MD resistance candidate genes, such as CTLA4, HDAC9 and CD72, were also found in our differentially expressed genes list. Moreover, we found that several intergroup specifically deregulated genes were involved in important biological processes and pathways, including B cell activation and Wnt signaling pathway. We conducted co-expression network using WGCNA and identified several hub genes that may play pivotal roles in MD resistance and tumorigenesis, e.g. CTLA4, SWAP70, CXCL12 and JCHAIN. According to the expression relationship between lncRNAs and MD resistance candidate mRNAs, five deregulated lncRNAs may implicate the chicken immunity by directly or indirectly regulating those hub genes. Conclusions: We profiled both lncRNA and mRNA expression patterns in MDV-infected chicken spleens. Expression variations of intergroup specifically deregulated genes engaged in important immune process likely contributed to robust immune system in the survivors. Some oncogenesis or MD resistance related genes deregulated between groups, like CTLA4, HDAC9 and CD72 were found. Co-expression network analysis manifested that lncRNAs may affect MD resistance and tumorigenesis in chicken spleens through their impact on expression of CTLA4, SWAP70 and some other genes that are critical in many important biological processes, such as B lymphocyte proliferation and activation.
2019-02-18 | GSE124133 | GEO