AJMB  Vol.2 No.3 , July 2012
Marek’s disease virus challenge induced immune-related gene expression and chicken repeat 1 (CR1) methylation alterations in chickens
Marek’s disease virus (MDV) challenge induces lymphoma in susceptible chickens. Host genes, especially immune related genes, are activated by the virus. DNA methylation is an epigenetic mechanism that governs gene transcription. In the present study, we found that expression of signal transducer and activator of transcription 1 (STAT1) was upregulated at 10 days post infection (dpi) in MD susceptible chickens, whereas interleukin 12A (IL12A) was elevated in both resistant and susceptible chickens. However, we did not observe MDV-induced DNA methylation variations at the promoter CpG islands (CGIs) in STAT1 and IL12A. Interestingly, the methylation levels at Chicken Repeat 1 (CR1), the transposable elements (TEs) located upstream of two genes, were different between resistant and susceptible chickens. Furthermore, a mutation was identified in the CR1 element near IL12A. The impact of the point mutation in transcriptional factor binding is to be examined in the near future.

Cite this paper
Tian, F. , Luo, J. , Zhang, H. , Chang, S. and Song, J. (2012) Marek’s disease virus challenge induced immune-related gene expression and chicken repeat 1 (CR1) methylation alterations in chickens. American Journal of Molecular Biology, 2, 232-241. doi: 10.4236/ajmb.2012.23024.
[1]   Davison, T.F., Nair, V. (2004) Marek's disease: an evolving problem. Amsterdam ; Boston: Elsevier.

[2]   Kaiser, P., Underwood, G.and Davison, F. (2003) Differential cytokine responses following Marek's disease virus infection of chickens differing in resistance to Marek's disease. Journal of Virology, 77, 762-768.

[3]   Abdul-Careem, M.F., Hunter, B.D., Sarson, A.J., Mayameei, A., Zhou, H.and Sharif ,S. (2006) Marek's disease virus-induced transient paralysis is associated with cytokine gene expression in the nervous system. Viral Immunolog, 19, 167-176.

[4]   Sarson, A.J., Parvizi, P., Lepp, D., Quinton, M.and Sharif, S. (2008) Transcriptional analysis of host responses to Marek's disease virus infection in genetically resistant and susceptible chickens. Animal Genetics, 39, 232-240.

[5]   Baylin, S.B., Ohm, J.E. (2006) Epigenetic gene silencing in cancer-a mechanism for early oncogenic pathway addiction? Nature Reviews Cancer, 6,107-116.

[6]   Luo, J., Yu, Y., Zhang, H., Tian, F., Chang, S., Cheng, H.H. and Song, J. (2011) Down-regulation of promoter methylation level of CD4 gene after MDV infection in MD-susceptible chicken line. BMC Proceedings 2011, 5 , S7.

[7]   Osterrieder, N., Kamil, J.P., Schumacher, D., Tischer, B.K. and Trapp, S. (2006) Marek's disease virus: from miasma to model. Nature Reviews Microbioloy, 4, 283-294.

[8]   Burch, J.B., Davis, D.L.and Haas, N.B. (1993) Chicken repeat 1 elements contain a pol-like open reading frame and belong to the non-long terminal repeat class of retrotransposons. Proceedings of National Academy of Science U S A, 90, 8199-8203.

[9]   Vandergon, T.L., Reitman, M. (1994) Evolution of chicken repeat 1 (CR1) elements: evidence for ancient subfamilies and multiple progenitors. Molecular Biology and Evolution . 11(6):886-898.

[10]   Hiller, L.W. (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature. 432, 695-716.

[11]   Wallis, J.W., Aerts, J., Groenen, M.A., Crooijmans, R.P., Layman, D., Graves, T.A., Scheer, D.E., Kremitzki, C., Fedele, M.J., Mudd, N.K. et al (2004) A physical map of the chicken genome. Nature, 432, 761-764.

[12]   Wong, G.K., Liu, B., Wang, J., Zhang, Y., Yang, X., Zhang, Z., Meng, Q., Zhou, J., Li, D., Zhang, J., et al (2004) A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms, Nature. 432, 717-722.

[13]   Feinberg, A.P., Tycko, B. (2004) The history of cancer epigenetics. Nature Reviews Cancer, 4,143-153.

[14]   Suter, C.M., Martin, D.I.and Ward, R.L. (2004) Hypomethylation of L1 retrotransposons in colorectal cancer and adjacent normal tissue. International Journal Colorectal Diseaase, 19, 95-101.

[15]   Bacon, L.D., Hunt, H.D.and Cheng, H.H. (2000) A review of the development of chicken lines to resolve genes determining resistance to diseases. Poultry Science, 79,1082-1093.

[16]   Tian, F., Luo, J., Zhang, H., Chang, S. and Song, J. (2012) MiRNA expression signatures induced by Marek's disease virus infection in chickens. Genomics, 99,152-159.

[17]   Heidari, M., Sarson, A.J., Huebner, M., Sharif, S., Kireev, D. and Zhou, H. (2010) Marek's disease virus-induced immunosuppression: array analysis of chicken immune response gene expression profiling. Viral Immunology, 23, 309-319.

[18]   Parvizi, P., Read, L.R., Abdul-Careem, M.F., Sarson, A.J., Lusty, C., Lambourne, M., Thanthrige-Don, N., Burgess, S.C.and Sharif, S. (2009) Cytokine gene expression in splenic CD4+ and CD8+ T cell subsets of genetically resistant and susceptible chickens infected with Marek's disease virus. Veterniary Immunology and Immunopathology, 132, 209-217.

[19]   Parvizi, P., Read, L., Abdul-Careem, M.F., Lusty, C. and Sharif, S. (2009) Cytokine gene expression in splenic CD4(+) and CD8(+) T-cell subsets of chickens infected with Marek's disease virus. Viral Immunology, 22, 31-38.

[20]   Heinemeyer, T., Wingender, E., Reuter, I., Hermjakob, H., Kel, A.E., Kel, O.V., Ignatieva, E.V., Ananko, E.A., Podkolodnaya, O.A., Kolpakov, F.A. et al (1998) Data-bases on transcriptional regulation: TRANSFAC, TRRD and COMPEL. Nucleic Acids Research, 26, 362-367.

[21]   Katze MG, He Y, Gale M, Jr.: Viruses and interferon: a fight for supremacy. Nat Rev Immunol 2002, 2(9):675-687.

[22]   Kalinski, P., Hilkens, C.M., Snijders, A., Snijdewint, F.G. and Kapsenberg, M.L. (1997) IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells. Journal of Immunology, 159, 28-35.

[23]   Heidari, M., Zhang, H.M. and Sharif, S. (2008) Marek's disease virus induces Th-2 activity during cytolytic infection. Viral Immunology, 21, 203-214.

[24]   Su, P.F., Lee, T.C., Lin, P.J., Lee, P.H., Jeng, Y.M., Chen, C.H., Liang, J.D., Chiou, L.L., Huang, G.T. and Lee, H.S. (2007) Differential DNA methylation associated with hepatitis B virus infection in hepatocellular carcinoma. Intertnational Journal of Cancer, 121, 1257-1264.

[25]   Tong, J.H., Tsang, R.K., Lo, K.W., Woo, J.K., Kwong, J., Chan, M.W., Chang, A.R., van Hasselt, C.A., Huang, D.P. and To, K.F. (2002) Quantitative Epstein-Barr virus DNA analysis and detection of gene promoter hypermethylation in nasopharyngeal (NP) brushing samples from patients with NP carcinoma. Clinic Cancer Research, 8, 2612-2619.

[26]   Doi, A., Park, I.H., Wen, B., Murakami, P., Aryee, M.J., Irizarry, R., Herb, B., Ladd-Acosta, C., Rho, J., Loewer, S. et al (2009) Differential methylation of tissue-and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts. Nature Genetics, 41, 1350-1353.

[27]   Jordan, I.K., Rogozin, I.B., Glazko, G.V. and Koonin, E.V. (2003) Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends in Genetics, 19, 68-72.

[28]   Merika, M., Orkin S.H. (1993) DNA-binding specificity of GATA family transcription factors. Molecular and Cellular Biology, 13, 3999-4010.

[29]   Huang, Z., Richmond, T.D., Muntean, A.G., Barber, D.L., Weiss, M.J. and Crispino, J.D. (2007) STAT1 promotes megakaryopoiesis downstream of GATA-1 in mice. Journal of Clinical Investigation, 117, 3890-3899.

[30]   Deng, G., Chen, A., Pong, E. and Kim, Y.S. (2001) Methylation in hMLH1 promoter interferes with its binding to transcription factor CBF and inhibits gene expression. Oncogene, 20, 7120-7127.

[31]   Lucas, M.E., Crider, K.S., Powell, D.R., Kapoor-Vazirani, P. and Vertino, P.M. (2009) Methylation-sensitive regulation of TMS1/ASC by the ETS factor, GA-binding protein-alpha. Journal of Biological Chemistry. 284,14698-709.

[32]   Yan, Q.W., Reed, E., Zhong, X.S., Thornton, K., Guo, Y.and Yu, J.J. (2006) MZF1 possesses a repressively regulatory function in ERCC1 expression. Biochemical Pharmacoogy, 71, 761-771.

[33]   Yang, Y., Contag, C.H., Felsher, D., Shachaf, C.M., Cao, Y., Herzenberg, L.A., Herzenberg, L.A. and Tung, J.W. (2004) The E47 transcription factor negatively regulates CD5 expression during thymocyte development. Proceedings of National Academy of Science U S A, 101, 3898-3902.

[34]   Curradi, M., Izzo, A., Badaracco, G. and Landsberger, N. (2002) Molecular mechanisms of gene silencing mediated by DNA methylation. Molecular and Cellular Biology, 22, 3157-3173.