Transcriptional analysis of host responses to Marek’s disease virus infection in genetically resistant and susceptible chickens

Abstract

Marek's disease virus (MDV) is a cell-associated oncogenic herpesvirus that targets B cells and T cells, inducing lymphoid tumours in chickens. Genetic resistance to Marek's disease (MD) is regulated in a polygenic fashion. In this study, we sought to compare the gene expression profiles following infection of birds that are genetically resistant or susceptible to MD (with the B21 and B19 haplotypes respectively at the MHC locus), including comparisons to uninfected controls. On days 4, 7, 14 and 21 post-infection, gene expression profiles in spleen tissue were obtained using a chicken immune-specific microarray. A number of genes showed significant (P <or= 0.05) differential expression across time and treatments. These included the chemokine AH221, B-cell marker Bu-1, IgG, IgA, IgM, MHC class II beta chain, granzyme A (GZMA) and signal transducers and activators of transcription 2 (STAT2) genes. In several comparisons, genes such as GZMA and STAT2 were induced in infected birds regardless of their genetic background. However, only immunoglobulin genes were differentially expressed by >or=2-fold in resistant compared with susceptible infected chickens. IgM and IgG were significantly induced on day 7 post-infection in susceptible chickens compared to resistant birds, whereas both of these genes were repressed in susceptible birds on day 14 post-infection. Overall, gene expression profiles in the chicken spleen observed after MDV infection were dependent on time and host genetic background. These gene expression profiles provide a platform for defining novel candidate genes for resistance or susceptibility to MD.

Systems Analysis of Immune Responses in Marek's Disease Virus-Infected Chickens Identifies a Gene Involved in Susceptibility and Highlights a Possible Novel Pathogenicity Mechanism

“…These included both type I (IFNA) and type II (IFNG) interferons (IFN), some interleukins and interleukin receptors (IL-6, IL13R2A, and IL-18), the proinflammatory chemokine CCLi7 (previously called ah221), genes involved in the interferon response (such as the signaling molecule interferon regulatory factor 1 [IRF1]), inducible nitric oxide synthase (NOS2A), the lymphocyte antigen Ly-6E precursor (SCA2), the quiescencespecific protein P20K, and the proinflammatory protease granzyme A (GZMA) (29,30,31,41).…”

“…In recent years, a small number of microarray experiments have been carried out to determine gene expression changes occurring during the host response to MDV infection and to identify genes involved in disease resistance (29,40,41). However, these have been on a much smaller scale and therefore are more limited in their findings.…”

Vaccination and Host Marek's Disease-Resistance Genotype Significantly Reduce Oncogenic <b><i>Gallid alphaherpesvirus 2</i></b> Telomere Integration in Host Birds

“…Host bird genetics contributes to MD resistance/susceptibility as well as the effectiveness of the MD vaccines [Bacon and Witter, 1994;Sarson et al, 2008;Chang et al, 2010Chang et al, , 2012. The chicken major histocompatibility complex (MHC) has long been known to have a major influence on MD disease incidence [Briles et al, 1983;Bacon, 1987;Schat et al, 1994;Bacon et al, 2000;Sarson et al, 2008;Miller and Taylor, 2016].…”

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

“…The high-throughput microarray is one of the widely used technologies in transcriptome studies (Haq et al, 2010;Liu et al, 2001;Sarson et al, 2008). The microarray technology was applied to analyze the global gene expression profile of CEF following GX0101∆LTR infection in the current study.…”