Abstract
Technologies used for genome analysis and whole genome sequencing are useful for us to understand genomic characterization and divergence. The Epstein-Barr virus (EBV) is an oncogenic virus that causes diverse diseases such as Burkitt’s lymphoma (BL), nasopharyngeal carcinoma (NPC), Hodgkin’s lymphoma (HL), and gastric carcinoma (GC). EBV genomes found in these diseases can be classified either by phases of EBV latency (type-I, -II, and -III latency) or types of EBNA2 sequence difference (type-I EBV, type-II EBV or EBV-1, EBV-2). EBV from EBV-transformed lymphoblastoid cell line (LCL) establishes type-III latency, EBV from NPC establishes type-II latency, and EBV from GC establishes type-I latency. However, other important factors play key roles in classifying numerous EBV strains because EBV genomes are highly diverse and not phylogenetically related to types of EBV-associated diseases. Herein, we first reviewed previous studies to describe molecular characteristics of EBV genomes. Then, using comparative and phylogenetic analyses, we phylogenetically analyzed molecular variations of EBV genomes and proteins. The review of previous studies and our phylogenetic analysis showed that EBV genomes and proteins were highly diverse regardless of types of EBV-associated diseases. Other factors should be considered in determining EBV taxonomy. This review will be helpful to understand complicated phylogenetic relationships of EBV genomes.
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Baer, R., Bankier, A.T., Biggin, M.D., Deininger, P.L., Farrell, P.J., Gibson, T.J., Hatfull, G., Hudson, G.S., Satchwell, S.C., Seguin, C., et al. 1984. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature 310, 207–211.
Chang, M.S. and Kim, W.H. 2005. Epstein-Barr virus in human malignancy: a special reference to Epstein-Barr virus associated gastric carcinoma. Cancer Res. Treat. 37, 257–267.
Chen, M.R. 2011. Epstein-Barr virus, the immune system, and associated diseases. Front. Microbiol. 2, 5.
Cheung, S.T., Leung, S.F., Lo, K.W., Chiu, K.W., Tam, J.S., Fok, T.F., Johnson, P.J., Lee, J.C., and Huang, D.P. 1998. Specific latent membrane protein 1 gene sequences in type 1 and type 2 Epstein- Barr virus from nasopharyngeal carcinoma in Hong Kong. Int. J. Cancer 76, 399–406.
Choi, S.J., Shin, Y.S., Kang, B.W., Kim, J.G., Won, K.J., Lieberman, P.M., Cho, H., and Kang, H. 2017. DNA hypermethylation induced by Epstein-Barr virus in the development of Epstein-Barr virus-associated gastric carcinoma. Arch. Pharm. Res. 40, 894–905.
Dambaugh, T., Hennessy, K., Chamnankit, L., and Kieff, E. 1984. U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2. Proc. Natl. Acad. Sci. USA 81, 7632–7636.
Dolan, A., Addison, C., Gatherer, D., Davison, A.J., and McGeoch, D.J. 2006. The genome of Epstein-Barr virus type 2 strain AG876. Virology 350, 164–170.
Frazer, K.A., Pachter, L., Poliakov, A., Rubin, E.M., and Dubchak, I. 2004. VISTA: computational tools for comparative genomics. Nucleic Acids Res. 32, W273–W279.
Gulley, M.L. 2001. Molecular diagnosis of Epstein-Barr virus-related diseases. J. Mol. Diagn. 3, 1–10.
Kanda, T., Furuse, Y., Oshitani, H., and Kiyono, T. 2016. Highly efficient CRISPR/Cas9-mediated cloning and functional characterization of gastric cancer-derived Epstein-Barr virus strains. J. Virol. 90, 4383–4393.
Kenney, S.C. and Mertz, J.E. 2014. Regulation of the latent-lytic switch in Epstein-Barr virus. Semin. Cancer Biol. 26, 60–68.
Kim, D.N., Chae, H.S., Oh, S.T., Kang, J.H., Park, C.H., Park, W.S., Takada, K., Lee, J.M., Lee, W.K., and Lee, S.K. 2007. Expression of viral microRNAs in Epstein-Barr virus-associated gastric carcinoma. J. Virol. 81, 1033–1036.
Kim, D.N., Seo, M.K., Choi, H., Kim, S.Y., Shin, H.J., Yoon, A.R., Tao, Q., Rha, S.Y., and Lee, S.K. 2013. Characterization of naturally Epstein-Barr virus-infected gastric carcinoma cell line YCCEL1. J. Gen. Virol. 94, 497–506.
Kwok, H., Tong, A.H., Lin, C.H., Lok, S., Farrell, P.J., Kwong, D.L., and Chiang, A.K. 2012. Genomic sequencing and comparative analysis of Epstein-Barr virus genome isolated from primary nasopharyngeal carcinoma biopsy. PLoS One 7, e36939.
Kwok, H., Wu, C.W., Palser, A.L., Kellam, P., Sham, P.C., Kwong, D.L., and Chiang, A.K. 2014. Genomic diversity of Epstein-Barr virus genomes isolated from primary nasopharyngeal carcinoma biopsy samples. J. Virol. 88, 10662–10672.
Lee, W., Hwang, Y.H., Lee, S.K., Subramanian, C., and Robertson, E.S. 2001. An Epstein-Barr virus isolated from a lymphoblastoid cell line has a 16-kilobase-pair deletion which includes gp350 and the Epstein-Barr virus nuclear antigen 3A. J. Virol. 75, 8556–8568.
Lin, Z., Wang, X., Strong, M.J., Concha, M., Baddoo, M., Xu, G., Baribault, C., Fewell, C., Hulme, W., Hedges, D., et al. 2013. Whole-genome sequencing of the Akata and Mutu Epstein-Barr virus strains. J. Virol. 87, 1172–1182.
Liu, P., Fang, X., Feng, Z., Guo, Y.M., Peng, R.J., Liu, T., Huang, Z., Feng, Y., Sun, X., Xiong, Z., et al. 2011. Direct sequencing and characterization of a clinical isolate of Epstein-Barr virus from nasopharyngeal carcinoma tissue by using next-generation sequencing technology. J. Virol. 85, 11291–11299.
Lo, K.W. and Huang, D.P. 2002. Genetic and epigenetic changes in nasopharyngeal carcinoma. Semin. Cancer Biol. 12, 451–462.
Matsusaka, K., Funata, S., Fukuyo, M., Seto, Y., Aburatani, H., Fukayama, M., and Kaneda, A. 2017. Epstein-Barr virus infection induces genome-wide de novo DNA methylation in non-neoplastic gastric epithelial cells. J. Pathol. 242, 391–399.
Mukhopadhyay, R. 2009. DNA sequencers: the next generation. Anal. Chem. 81, 1736–1740.
Murata, T. 2014. Regulation of Epstein-Barr virus reactivation from latency. Microbiol. Immunol. 58, 307–317.
Murata, T. and Tsurumi, T. 2014. Switching of EBV cycles between latent and lytic states. Rev. Med. Virol. 24, 142–153.
Neves, M., Marinho-Dias, J., Ribeiro, J., and Sousa, H. 2017. Epstein-Barr virus strains and variations: Geographic or disease-specific variants? J. Med. Virol. 89, 373–387.
Odumade, O.A., Hogquist, K.A., and Balfour, H.H. 2011. Progress and problems in understanding and managing primary Epstein- Barr virus infections. Clin. Microbiol. Rev. 24, 193–209.
Ohga, S., Nomura, A., Takada, H., and Hara, T. 2002. Immunological aspects of Epstein-Barr virus infection. Crit. Rev. Oncol. Hematol. 44, 203–215.
Palser, A.L., Grayson, N.E., White, R.E., Corton, C., Correia, S., Ba Abdullah, M.M., Watson, S.J., Cotten, M., Arrand, J.R., Murray, P.G., et al. 2015. Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection. J. Virol. 89, 5222–5237.
Parker, B.D., Bankier, A., Satchwell, S., Barrell, B., and Farrell, P.J. 1990. Sequence and transcription of Raji Epstein-Barr virus DNA spanning the B95-8 deletion region. Virology 179, 339–346.
Qiu, J., Cosmopoulos, K., Pegtel, M., Hopmans, E., Murray, P., Middeldorp, J., Shapiro, M., and Thorley-Lawson, D.A. 2011. A novel persistence associated EBV miRNA expression profile is disrupted in neoplasia. PLoS Pathog. 7, e1002193.
Ressing, M.E., van Gent, M., Gram, A.M., Hooykaas, M.J., Piersma, S.J., and Wiertz, E.J. 2015. Immune evasion by Epstein-Barr virus. Curr. Top. Microbiol. Immunol. 391, 355–381.
Robertson, E.S., Ooka, T., and Kieff, E.D. 1996. Epstein-Barr virus vectors for gene delivery to B lymphocytes. Proc. Natl. Acad. Sci. USA 93, 11334–11340.
Sample, J., Young, L., Martin, B., Chatman, T., Kieff, E., Rickinson, A., and Kieff, E. 1990. Epstein-Barr virus types 1 and 2 differ in their EBNA-3A, EBNA-3B, and EBNA-3C genes. J. Virol. 64, 4084–4092.
Shibata, D., Tokunaga, M., Uemura, Y., Sato, E., Tanaka, S., and Weiss, L.M. 1991. Association of Epstein-Barr virus with undifferentiated gastric carcinomas with intense lymphoid infiltration. Lymphoepithelioma-like carcinoma. Am. J. Pathol. 139, 469–474.
Song, K.A., Yang, S.D., Hwang, J., Kim, J.I., and Kang, M.S. 2015. The full-length DNA sequence of Epstein Barr virus from a human gastric carcinoma cell line, SNU-719. Virus Genes 51, 329–337.
Tamura, K., Peterson, D., Peterson, N., Stecher, G., Nei, M., and Kumar, S. 2011. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 28, 2731–2739.
Tso, K.K., Yip, K.Y., Mak, C.K., Chung, G.T., Lee, S.D., Cheung, S.T., To, K.F., and Lo, K.W. 2013. Complete genomic sequence of Epstein-Barr virus in nasopharyngeal carcinoma cell line C666-1. Infect. Agents Cancer 8, 29.
Tsurumi, T., Fujita, M., and Kudoh, A. 2005. Latent and lytic Epstein- Barr virus replication strategies. Rev. Med. Virol. 15, 3–15.
Tzellos, S. and Farrell, P.J. 2012. Epstein-Barr virus sequence variation–biology and disease. Pathogens 1, 156–174.
Wu, C.C., Fang, C.Y., Cheng, Y.J., Hsu, H.Y., Chou, S.P., Huang, S.Y., Tsai, C.H., and Chen, J.Y. 2017. Inhibition of Epstein-Barr virus reactivation by the flavonoid apigenin. J. Biomed. Sci. 24, 2.
Xiao, K., Yu, Z., Li, X., Li, X., Tang, K., Tu, C., Qi, P., Liao, Q., Chen, P., Zeng, Z., et al. 2016. Genome-wide analysis of Epstein-Barr virus (EBV) integration and strain in C666-1 and Raji cells. J. Cancer 7, 214–224.
Young, L.S., Dawson, C.W., and Eliopoulos, A.G. 2000. The expression and function of Epstein-Barr virus encoded latent genes. Mol. Pathol. 53, 238–247.
Young, L.S. and Rickinson, A.B. 2004. Epstein-Barr virus: 40 years on. Nat. Rev. Cancer 4, 757–768.
Young, L.S., Yap, L.F., and Murray, P.G. 2016. Epstein-Barr virus: more than 50 years old and still providing surprises. Nat. Rev. Cancer 16, 789–802.
Zeng, M.S., Li, D.J., Liu, Q.L., Song, L.B., Li, M.Z., Zhang, R.H., Yu, X.J., Wang, H.M., Ernberg, I., and Zeng, Y.X. 2005. Genomic sequence analysis of Epstein-Barr virus strain GD1 from a nasopharyngeal carcinoma patient. J. Virol. 79, 15323–15330.
Zhang, C.X., Decaussin, G., Daillie, J., and Ooka, T. 1988. Altered expression of two Epstein-Barr virus early genes localized in BamHI-A in nonproducer Raji cells. J. Virol. 62, 1862–1869.
Zhang, X.S., Song, K.H., Mai, H.Q., Jia, W.H., Feng, B.J., Xia, J.C., Zhang, R.H., Huang, L.X., Yu, X.J., Feng, Q.S., et al. 2002. The 30 bp deletion variant: a polymorphism of latent membrane protein 1 prevalent in endemic and non-endemic areas of nasopharyngeal carcinomas in China. Cancer Lett. 176, 65–73.
Zhou, L., Chen, J.N., Qiu, X.M., Pan, Y.H., Zhang, Z.G., and Shao, C.K. 2017. Comparative analysis of 22 Epstein-Barr virus genomes from diseased and healthy individuals. J. Gen. Virol. 98, 96–107.
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Choi, S.J., Jung, S.W., Huh, S. et al. Phylogenetic comparison of Epstein-Barr virus genomes. J Microbiol. 56, 525–533 (2018). https://doi.org/10.1007/s12275-018-8039-x
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DOI: https://doi.org/10.1007/s12275-018-8039-x