Unknown,Transcriptomics,Genomics,Proteomics

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The Transcriptional Landscape of Marek’s Disease Virus in Primary Chicken B Cells Reveals Novel Splice Variants and Genes

ABSTRACT: Marek's disease virus (MDV) belongs to the alphaherpesviruses and is the causative agent of fatal T cell lymphomas in chickens. Aftermaths of MDV infections lead to substantial losses in poultry industry and there is evidence that MDV constantly evolves towards higher virulence. This study takes a detailed look at the very first step of the viral life cycle in the host: the infection of B cells. Recently, it has become possible to culture and infect primary chicken B cells ex vivo, enabling us to apply those cells to RNAseq analysis. Here, we provide novel insights into MDV gene expression profiles and post-transcriptional modifications of this important poultry pathogen in its primary target cells for lytic replication. Remarkably enough, we could detect a novel hypothetical MDV gene, identify multicistronic transcripts and previously unannotated splice forms. These findings lay the foundation for future research on MDV replication and pathogenesis and the developed bioinformatics pipeline can be easily transferred to other herpesviruses or large DNA viruses to identify unknown transcript isoforms and associated motifs.

INSTRUMENT(S): Ion Torrent S5 XL

ORGANISM(S): Gallus gallus

SUBMITTER: Ahmed Kheimar

PROVIDER: E-MTAB-7772 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The Transcriptional Landscape of Marek's Disease Virus in Primary Chicken B Cells Reveals Novel Splice Variants and Genes.

Bertzbach Luca D LD Pfaff Florian F Pauker Viktoria I VI Kheimar Ahmed M AM Höper Dirk D Härtle Sonja S Karger Axel A Kaufer Benedikt B BB

Viruses 20190316 3

Marek's disease virus (MDV) is an oncogenic alphaherpesvirus that infects chickens and poses a serious threat to poultry health. In infected animals, MDV efficiently replicates in B cells in various lymphoid organs. Despite many years of research, the viral transcriptome in primary target cells of MDV remained unknown. In this study, we uncovered the transcriptional landscape of the very virulent RB1B strain and the attenuated CVI988/Rispens vaccine strain in primary chicken B cells using high-t ...[more]

PMID: 30884829

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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

Dataset Information

The Transcriptional Landscape of Marek’s Disease Virus in Primary Chicken B Cells Reveals Novel Splice Variants and Genes

Publications

The Transcriptional Landscape of Marek's Disease Virus in Primary Chicken B Cells Reveals Novel Splice Variants and Genes.

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