Histone modifications induced by MDV infection at early cytolytic and latency phases.

Apratim Mitra,Jiuzhou Song,Huanmin Zhang,Yulan Gu,Juan Luo,Kairong Cui,Yanghua He,Keji Zhao

doi:10.1186/s12864-015-1492-6

Abstract

BackgroundMarek’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.ResultsIn 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.ConclusionOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1492-6) contains supplementary material, which is available to authorized users.

Highlights

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
Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) was performed on bursal tissues obtained from MD-resistant line L63 and MD-susceptible line L72 chickens
The changes induced by MDV infection likely involved subtle variations at specific genomic

Summary

Introduction

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 can be divided into three major stages: an early cytolytic phase, which occurs between 3 and 6 days post infection (dpi), is characterized by the infection of B lymphocytes, the first major targets of MDV. Cytolytic infection initiates in the spleen before spreading to other lymphoid organs, which lag behind by a day. This is accompanied by significant cytolysis of B and T lymphocytes in addition to varying levels of inflammatory response. In MD-susceptible chickens, a second wave of cytolytic infection around 1421dpi results in marked inflammation, severe atrophy of bursa and thymus and permanent immunosuppression

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