DNA Methylation Fluctuation Induced by Virus Infection Differs between MD-resistant and -susceptible Chickens.

Juan Luo,Ying Yu,Jiuzhou Song,Fei Tian,Huanmin Zhang,Shuang Chang

doi:10.3389/fgene.2012.00020

Abstract

Marek’s disease (MD) is a lymphoproliferative disease induced by Marek’s disease virus (MDV) infection. To augment vaccination measures in MD control, host genetic resistant to MD becomes obviously more and more important. To elucidate the mechanism of MD-resistance, most of researches were focused on the genetic differences between resistant and susceptible chickens. However, epigenetic features between MD resistant and susceptible chickens are poorly characterized. Using bisulfite pyrosequencing method, we found some candidate genes have higher promoter methylation in the MD-susceptible (L72) chickens than in the MD-resistant (L63) chickens. The hypermethylated genes, involved in cellular component organization, responding to stimulus, cell adhesion, and immune system process, may play important role in susceptibility to disease by deregulation of these genes. MDV infection induced the expression changes of all three methyltransferases genes (DNMT1, DNMT3a, and DNMT3b) in both lines of chickens. The DNMT1 was up-regulated in L72, whereas the DNMT3b was down-regulated in L63 at 21 dpi. Interestingly, a dynamic change of promoter methylation was observed during MDV life cycle. Some genes, including HDAC9, GH, STAT1, CIITA, FABP3, LATS2, and H2Ac, showed differential methylation behaviors between the two lines of chickens. In summary, the findings from this study suggested that DNA methylation heterogeneity and MDV infection induced methylation alterations differences existed between the two lines of chickens. Therefore, it is suggested that epigenetic mechanisms may be involved in modulating the resistance and/or susceptibility to MD in chickens.

Highlights

Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by Marek’s disease virus (MDV) with pathological features including mononuclear cell-infiltration in the peripheral nerves, skin, and muscle (Davison and Nair, 2004)
MDV life cycle in its host can be divided into four phases, including an early cytolytic phase from 2 to 7 days post infection, a latency phase around 7–10 dpi, a late cytolytic phase starting from 18 dpi and a proliferation phase after 28 dpi (Calnek, 1986, 2001)
To advance the understanding of functional patterns of DNA methylation in disease resistance or susceptibility, we extended the scope of examination to 18 interested genes, which include STAT1, CIITA, NK-lysin, CD44, IL12, and GH1 that the expression levels of these gene are alterable upon MDV challenge (Liu et al, 2001; Abdul-Careem et al, 2006; Parcells and Burgess, 2008; Sarson et al, 2008a,b; Heidari et al, 2010; Thanthrige-Don et al, 2010)

Summary

Introduction

Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by Marek’s disease virus (MDV) with pathological features including mononuclear cell-infiltration in the peripheral nerves, skin, and muscle (Davison and Nair, 2004). Since the inheritance and resistance to MD was first observed (Asmundson and Biely, 1932), MD-resistant and -susceptible chickens have been bred by those including Stone (lines 6 and 7; Bacon et al, 2000), Hutt, and Cole (lines N and P; Davison and Nair, 2004). The selection of genetically disease resistant chickens is especially important in MD control. A better understanding in the mechanisms of MD-resistance and -susceptibility should be of great value in developing better strategies to further prevent and control MD

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Conclusion