Dynamic Changes in the Splenic Transcriptome of Chickens during the Early Infection and Progress of Marek\u2019s Disease

Lu Dang,Jun Luo,Gai-Ping Zhang,Pu Zhao,Man Teng,Xiu-Jie Li,Rui-Guang Deng,Sheng-Ming Ma,Hua-Wei Li,Hui-Zhen Li

doi:10.1038/s41598-017-11304-y

Abstract

Gallid alphaherpesvirus 2 (GaHV2) is an oncogenic avian herpesvirus inducing Marek’s disease (MD) and rapid-onset T-cell lymphomas. To reveal molecular events in MD pathogenesis and tumorigenesis, the dynamic splenic transcriptome of GaHV2-infected chickens during early infection and pathogenic phases has been determined utilizing RNA-seq. Based on the significant differentially expressed genes (DEGs), analysis of gene ontology, KEGG pathway and protein-protein interaction network has demonstrated that the molecular events happening during GaHV2 infection are highly relevant to the disease course. In the ‘Cornell Model’ description of MD, innate immune responses and inflammatory responses were established at early cytolytic phase but persisted until lymphoma formation. Humoral immunity in contrast began to play a role firstly in the intestinal system and started at late cytolytic phase. Neurological damage caused by GaHV2 is first seen in early cytolytic phase and is then sustained throughout the following phases over a long time period. During the proliferative phase many pathways associated with transcription and/or translation were significantly enriched, reflecting the cell transformation and lymphoma formation. Our work provides an overall view of host responses to GaHV2 infection and offers a meaningful basis for further studies of MD biology.

Highlights

Marek’s disease (MD) is a major infectious disease affecting poultry health worldwide and is responsible for an approximate annual global economic losses of $2 billion[1]
MD pathogenesis is very complex and the natural course of the disease following infection has been well established as the ‘Cornell Model’[4, 5]
This study has provided the observations on the transcriptional changes in the host’s response to Gallid alphaherpesvirus 2 (GaHV2) infection and the progression of MD

Summary

Introduction

Marek’s disease (MD) is a major infectious disease affecting poultry health worldwide and is responsible for an approximate annual global economic losses of $2 billion[1]. The available chicken genome database[6] and microarrays[7] have become useful tools to study the gene and protein expression profiles of GaHV2-host interaction and for further revealing the molecular mechanisms involved in the pathogenic and tumorigenic responses to GaHV2 infection. Microarray analysis has been performed in vitro of the interactions between host cells and GaHV2, such as in the primary chicken embryo fibroblasts (CEFs) and the transformed cell line DF-18, 9 This technology has been used to investigate gene www.nature.com/scientificreports/. Based on the high-throughput technology, the dynamic and differential gene expression profiles obtained from GaHV2-infected chicken spleens will provide an important basis and more valuable information for future studies on the molecular mechanisms of MD pathogenesis and tumorigenesis

Methods

Results

Conclusion