Transcriptional Profiling of MEq-Dependent Genes in Marek’s Disease Resistant and Susceptible Inbred Chicken Lines

Abstract

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 to 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 and cells from MD resistant or susceptible birds, we compared the response to infection with either wild type MDV or a nononcogenic recombinant lacking mEq. As a result, we identified a number of specific genes and pathways associated with either MD resistance or susceptibility. Additionally, integrating prior information from ChIP-seq, microarray analysis, and SNPs exhibiting allele-specific expression (ASE) in response to MDV infection, we were able to provide evidence for 24 genes that are polymorphic within mEq binding sites are likely to account for gene expression in an allele-specific manner and potentially for the underlying genetic differences in MD incidence.

Sodium tanshinone IIA sulfonate affects Marek’s disease virus replication by inhibiting gB expression

“…However, vaccination could not prevent MDV from spreading in vaccinated birds (Subramaniam et al, 2013). Thus, new approach is needed to eliminate MD.…”

Transcriptome Analysis of Chicken Embryo Fibroblast Cell Infected with Marek’s Disease Virus of GX0101 ∆ LTR

“…Several studies have been performed to identify the gene expression profile in in-vivo and in-vitro MDV infections using microarray analysis (Yonash et al, 1999;Morgan et al, 2001;Sarson et al, 2006;Kano et al, 2009;Heidari et al, 2010;Smith et al, 2011;Lian et al, 2012, Subramaniam et al, 2013.. The molecular mechanism of the host response to GX0101∆LTR MDV was elucidated in the current study.…”

“…MDV infection induced gene expression. It has been reported that more genes are up-regulated in CEF at 24, 48, and 96 h post MDV infection in both MD-resistant and -susceptible chicken lines (Subramaniam et al, 2013). More upregulated genes have been observed in the spleen at 2 and 5 days post MDV infection (Smith et al, 2011).…”

“…The high-throughput microarray is one of most widely-used technologies to identify the transcriptome associated with a specific trait Lee et al, 2010;Li et al, 2010;Li et al, 2011;Sandford et al, 2011, Allen et al, 2012Sandford et al, 2012, Subramaniam et al, 2013. Several studies have been performed to identify the gene expression profile in in-vivo and in-vitro MDV infections using microarray analysis (Yonash et al, 1999;Morgan et al, 2001;Sarson et al, 2006;Kano et al, 2009;Heidari et al, 2010;Smith et al, 2011;Lian et al, 2012, Subramaniam et al, 2013..…”

“…The molecular mechanism of the host response to GX0101∆LTR MDV was elucidated in the current study. The CEF is a reasonable model for studying the reaction to MDV infection (Subramaniam et al, 2013). MDV infection includes the three following stages: early cytolytic infection starting at 2-7 dpi (day post infection), a latent phage initiated around 7-10 dpi, and a late cytolytic phase causing inflammation and transformation of latently-infected lymphocytes into tumor cells triggered between 14 and 21 dpi (Calnek, 1986, Calnek, 2001).…”