Temporal transcriptome changes induced by MDV in marek's disease-resistant and -susceptible inbred chickens

Abstract

BackgroundMarek's disease (MD) is a lymphoproliferative disease in chickens caused by Marek's disease virus (MDV) and characterized by T cell lymphoma and infiltration of lymphoid cells into various organs such as liver, spleen, peripheral nerves and muscle. Resistance to MD and disease risk have long been thought to be influenced both by genetic and environmental factors, the combination of which contributes to the observed outcome in an individual. We hypothesize that after MDV infection, genes related to MD-resistance or -susceptibility may exhibit different trends in transcriptional activity in chicken lines having a varying degree of resistance to MD.ResultsIn order to study the mechanisms of resistance and susceptibility to MD, we performed genome-wide temporal expression analysis in spleen tissues from MD-resistant line 63, susceptible line 72 and recombinant congenic strain M (RCS-M) that has a phenotype intermediate between lines 63 and 72 after MDV infection. Three time points of the MDV life cycle in chicken were selected for study: 5 days post infection (dpi), 10dpi and 21dpi, representing the early cytolytic, latent and late cytolytic stages, respectively. We observed similar gene expression profiles at the three time points in line 63 and RCS-M chickens that are both different from line 72. Pathway analysis using Ingenuity Pathway Analysis (IPA) showed that MDV can broadly influence the chickens irrespective of whether they are resistant or susceptible to MD. However, some pathways like cardiac arrhythmia and cardiovascular disease were found to be affected only in line 72; while some networks related to cell-mediated immune response and antigen presentation were enriched only in line 63 and RCS-M. We identified 78 and 30 candidate genes associated with MD resistance, at 10 and 21dpi respectively, by considering genes having the same trend of expression change after MDV infection in lines 63 and RCS-M. On the other hand, by considering genes with the same trend of expression change after MDV infection in lines 72 and RCS-M, we identified 78 and 43 genes at 10 and 21dpi, respectively, which may be associated with MD-susceptibility.ConclusionsBy testing temporal transcriptome changes using three representative chicken lines with different resistance to MD, we identified 108 candidate genes for MD-resistance and 121 candidate genes for MD-susceptibility over the three time points. Genes included in our resistance or susceptibility genes lists that are also involved in more than 5 biofunctions, such as CD8α, IL8, USP18, and CTLA4, are considered to be important genes involved in MD-resistance or -susceptibility. We were also able to identify several biofunctions related with immune response that we believe play an important role in MD-resistance.

Genomic Variation between Genetic Lines of White Leghorns Differed in Resistance to Marek’s Disease

“…The same SNP-fingerprint showed three RCS (RCS-B, RCS-M, and RCS-S) were more different from line 7 2 than line 6 3 as expected (Figure 3). Our recent study on gene expression profiling indicated that global gene expressions were significantly different between the chickens of lines 6 3 and 7 2 as well [36]. In addition to genetic differences, epigenetic differences now have been found to commonly exist between the two lines of chickens.…”

“…Earlier studies showed the primary lymphoid organ size and IgG level differ between the lines 6 3 and 7 2 [34,35]. Data from our recent collaborative studies showed that profiles of global gene expression with or without MDV challenge differ between the highly inbred line 6 3 and 7 2 and one recombinant congenic strain [36]. Using miRNA microarray, it was demonstrated that miRNAs were differentially expressed between line 6 3 and 7 2 chickens post MDV challenge [37].…”

DNMT gene expression and methylome in Marek’s disease resistant and susceptible chickens prior to and following infection by MDV

“…Our previous studies revealed that DNMTs were differentially expressed in the line 6 3 and line 7 2 chickens, 14 especially at 21 DPI, when the virus was reactivated from the latent stage. 6,15,16 The results point to a profound distinction between epigenetic profiles and expression of selected genes in line 6 3 and 7 2 chickens. The interesting finding that many of these differences, particularly in response to MDV challenge, affect genes of the immune system or tumor progression and related pathways provides a strong rationale for pursuit of our hypothesis that epigenetic signatures are associated with resistance or susceptibility of MDV induced tumorigenesis.…”

Genome-Wide Epigenetic Studies in Chicken: A Review

“…Interestingly, these comparative analyses revealed differentially enriched regions between susceptible and resistant chicken lines [85,86], suggesting the existence of an "epigenetic signature" for disease susceptibility. Moreover, Song and collaborators demonstrated that the HPTM profile was modulated after infection at the loci of genes involved in the immune system response [84], corresponding to expression changes after infection [88]. For example, at the locus of CD8α in spleen (for which expression was slightly or highly increased after infection in susceptible and resistant chicken lines, respectively), H3K4me3 was increased concomitantly to gene expression depending on the line [84].…”