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

Abstract

Marek’s disease (MD) is characterized as a T cell lymphoma induced by a cell-associated α-herpesvirus, Marek’s disease virus type 1 (MDV1). As with many viral infectious diseases, DNA methylation variations were observed in the progression of MD; these variations are thought to play an important role in host-virus interactions. We observed that DNA methyltransferase 3a (DNMT3a) and 3b (DNMT3b) were differentially expressed in chicken MD-resistant line 6₃ and MD-susceptible line 7₂ at 21 d after MDV infection. To better understand the role of methylation variation induced by MDV infection in both chicken lines, we mapped the genome-wide DNA methylation profiles in each line using Methyl-MAPS (methylation mapping analysis by paired-end sequencing). Collectively, the data sets collected in this study provide a more comprehensive picture of the chicken methylome. Overall, methylation levels were reduced in chickens from the resistant line 6₃ after MDV infection. We identified 11,512 infection-induced differential methylation regions (iDMRs). The number of iDMRs was larger in line 7₂ than in line 6₃, and most of iDMRs found in line 6₃ were overlapped with the iDMRs found in line 7₂. We further showed that in vitro methylation levels were associated with MDV replication, and found that MDV propagation in the infected cells was restricted by pharmacological inhibition of DNA methylation. Our results suggest that DNA methylation in the host may be associated with disease resistance or susceptibility. The methylation variations induced by viral infection may consequentially change the host transcriptome and result in diverse disease outcomes.

Keywords: :

• DNA methylation
• Marek’s disease
• chicken
• epigenetics
• tumor
• viral infection

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

Thanks Dr. Yanghua He for figures and Dr. Hans H. Cheng for the precious discussion of this manuscript.

Author’s contributions

FT and JH performed Methyl-MAPS experiment, did the validation of the results by Q-PCR, analyzed some of the result and wrote the paper. FZ, NV and JE analyzed the data. ZH did the microarray experiment and collected the samples and helped revised the manuscript. ZKJ and JZS designed and revised this paper.