Identification of N-acetylglucosaminyltranferase-IV as a modifier of Epstein-Barr virus BZLF1 activity


Epstein-Barr virus is a prevalent human herpesvirus, with about 95% of the world’s adult population positive for anti-EBV antigen antibodies. After the initial infection and production of new virus particles, the virus may enter a latent state within a subset of cells, and therefore can remain within the host indefinitely. Epstein-Barr virus contributes to a variety of diseases, including many types of cancers. We have created a model system in Drosophila melanogaster to study the effect of expression of the Epstein-Barr virus protein BZLF1, and to identify cellular proteins that mediate BZLF1 activity. Here we present the results of a genetic screen that determined that the Drosophila melanogaster CG9384 gene (an N-acetylglucosaminyl-transferase) is a significant modulator of BZLF1 activity and EBV early lytic replication.

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Adamson, A. (2013) Identification of N-acetylglucosaminyltranferase-IV as a modifier of Epstein-Barr virus BZLF1 activity. Open Journal of Genetics, 3, 1-5. doi: 10.4236/ojgen.2013.31001.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Rickinson, A.B. and Kieff, E. (2007) Epstein-Barr virus. In: Knipe, D.M. and Howley, P.M., Eds., Field’s Virology, Lippincott Williams & Wilkins, Philadelphia, 2655-2700.
[2] Kieff, E. and Rickinson, A.B. (2007) Epstein-Barr virus and its replication. In: Field’s Virology, Lippincott Williams & Wilkins, Philadelphia, 2603-2654.
[3] Adamson, A.L. and Kenney, S. (1999) The Epstein-Barr virus BZLF1 protein interacts physically and functionally with the histone acetylase CREB-binding protein. Journal of virology, 73, 6551-6518.
[4] Bowling, B.L. and Adamson, A.L. (2006) Functional interactions between the Epstein-Barr virus BZLF1 protein and the promyelocytic leukemia protein. Virus Research, 117, 244-253. doi:10.1016/j.virusres.2005.10.018
[5] Adamson, A.L., Wright, N. and LaJeunesse, D.R. (2005) Modeling early Epstein-Barr virus infection in Drosophila melanogaster: The BZLF1 protein. Genetics, 171, 1125-1135. doi:10.1534/genetics.105.042572
[6] Hay, B.A., Wolff, T. and Rubin, G. (1994) Expression of baculovirus P35 prevents cell death in Drosophila. Development (Cambridge, England), 120, 2121-2129.
[7] Adamson, A.L. and LaJeunesse, D. (2012) A study of Epstein-Barr virus BRLF1 activity in a Drosophila model system. TSWJ 2012, 1-9.
[8] Taniguchi, N. and Korekane, H. (2011) Branched N-glycans and their implications for cell adhesion, signaling and clinical applications for cancer biomarkers and in therapeutics. BMB Reports, 44, 772-781. doi:10.5483/BMBRep.2011.44.12.772
[9] Gleeson, P.A. and Schachter, H. (1983) Control of glycoprotein synthesis. The Journal of Biological Chemistry, 258, 6162-6173.
[10] Ide, Y., Miyoshi, E., Nakagawa, T., Gu, J., Tanemura, M., Nishida, T., Ito, T., Yamamoto, H., Kozutsumi, Y. and Taniguchi, N. (2006) Aberrant expression of N-acetylglucosaminyltransferase-IVa and IVb (GnT-IVa and b) in pancreatic cancer. Biochemical and Biophysical Research Communications, 341, 478-482. doi:10.1016/j.bbrc.2005.12.208
[11] Nan, B.C., Shao, D.M., Chen, H.L., Huang, Y., Gu, J.X., Zhang, Y.B. and Wu, Z.G. (1998) Alteration of N-acetylglucosaminyltransferases in pancreatic carcinoma. Glycoconjugate Journal, 15, 1033-1037. doi:10.1023/A:1006950311937
[12] D’Arrigo, A., Belluco, C., Ambrosi, A., Digito, M., Esposito, G., Bertola, A., Fabris, M., Nofrate, V., Mammano, E., Leon, A., Nitti, D. and Lise, M. (2005) Metastatic transcriptional pattern revealed by gene expression profiling in primary colorectal carcinoma. International Journal of Cancer, 115, 256-262. doi:10.1002/ijc.20883
[13] Zhu, T.Y., Chen, H.L., Gu, J.X., Zhang, Y.F., Zhang, Y.K. and Zhang, R.A. (1997) Changes in N-acetylglucosaminyltransferase III, IV and V in renal cell carcinoma. Journal of Cancer Research and Clinical Oncology, 123, 296-299.
[14] McQuilton, P., St. Pierre, S.E., Thurmond, J. and Consortium, T.F. (2012) FlyBase 101—The basics of navigating FlyBase. Nucleic Acids Research, 40, D706-D714. doi:10.1093/nar/gkr1030
[15] Calderwood, M.A., Holthaus, A.M. and Johannsen, E. (2008) The Epstein-Barr virus LF2 protein inhibits viral replication. Journal of Virology, 82, 8509-19. doi:10.1128/JVI.00315-08
[16] Liu, S., Li, H., Chen, L., Yang, L., Li, L., Tao, Y., Li, W., Li, Z., Liu, H., Tang, M., Bode, A.M., Dong, Z. and Cao, Y. (2012) (-)-Epigallocatechin-3-gallate inhibition of Epstein-Barr virus spontaneous lytic infection involves ERK1/2 and PI3-K/Akt signaling in EBV-positive cells. Carcinogenesis.
[17] Adamson, A.L., Darr, D., Holley-Guthrie, E., Johnson, R.A., Mauser, A., Swenson, J. and Kenney, S. (2000) Epstein-Barr virus immediate-early proteins BZLF1 and BRLF1 activate the ATF2 transcription factor by increasing the levels of phosphorylated p38 and c-Jun Nterminal kinases. Journal of Virology, 74, 1224-1233. doi:10.1128/JVI.74.3.1224-1233.2000
[18] Takamatsu, S., Antonopoulos, A., Ohtsubo, K., Ditto, D., Chiba, Y., Le, D.T., Morris, H.R., Haslam, S.M., Dell, A., Marth, J.D. and Taniguchi, N. (2010) Physiological and glycomic characterization of N-acetylglucosaminyltransferase-IVa and -IVb double deficient mice. Glycobiology, 20, 485-497. doi:10.1093/glycob/cwp200
[19] Brinkmann, M.M. and Schulz, T.F. (2006) Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae. The Journal of General Virology, 87, 1047-1074. doi:10.1099/vir.0.81598-0
[20] Izumi, K.M. (2004) Epstein-Barr virus signal transduction and B-lymphocyte growth transformation. Progress in Molecular and Subcellular Biology, 36, 269-288.
[21] Mosialos, G. (2001) Cytokine signaling and Epstein-Barr virus-mediated cell transformation. Cytokine & Growth Factor Reviews, 12, 259-270. doi:10.1016/S1359-6101(00)00035-6
[22] Bryant, H. and Farrell, P.J. (2002) Signal transduction and transcription factor modification during reactivation of Epstein-Barr virus from latency. Journal of Virology, 76, 10290-10298. doi:10.1128/JVI.76.20.10290-10298.2002

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