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Efficient Epstein-Barr Virus Progeny Production Mediated by Cancer-Derived LMP1 and Virally-Encoded microRNAs

1
Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan
2
Division of Cancer Cell Regulation, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
3
Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan
4
Department of Head and Neck Surgery, Asahi University Hospital, Gifu 500-8523, Japan
*
Author to whom correspondence should be addressed.
Microorganisms 2019, 7(5), 119; https://doi.org/10.3390/microorganisms7050119
Received: 26 March 2019 / Revised: 25 April 2019 / Accepted: 28 April 2019 / Published: 30 April 2019
(This article belongs to the Special Issue Recent Advances in Understanding Epstein-Barr Virus)
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Abstract

Epstein-Barr virus (EBV) genomes, particularly their latent genes, are heterogeneous among strains. The heterogeneity of EBV-encoded latent membrane protein 1 (LMP1) raises the question of whether there are functional differences between LMP1 expressed by cancer-associated EBV and that by non-cancerous strains. Here, we used bacterial artificial chromosome (BAC)-cloned EBV genomes retaining all virally encoded microRNA (miRNA) genes to investigate the functions of cancer-derived LMP1 in the context of the EBV genome. HEK293 cells were stably transfected with EBV-BAC clone DNAs encoding either nasopharyngeal carcinoma (NPC)-derived CAO-LMP1 (LMP1CAO) or LMP1 from a prototype B95-8 strain of EBV (LMP1B95-8). When an EBV-BAC clone DNA encoding LMP1CAO was stably transfected into HEK293 cells, it generated many more stable transformants than the control clone encoding LMP1B95-8. Furthermore, stably transfected HEK293 cells exhibited highly efficient production of progeny virus. Importantly, deletion of the clustered viral miRNA genes compromised the ability to produce progeny viruses. These results indicate that cancer-derived LMP1 and viral miRNAs together are necessary for efficient production of progeny virus, and that the resulting increase in efficiency contributes to EBV-mediated epithelial carcinogenesis. View Full-Text
Keywords: Epstein-Barr virus; Nasopharyngeal carcinoma; LMP1; BART; microRNA Epstein-Barr virus; Nasopharyngeal carcinoma; LMP1; BART; microRNA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Yajima, M.; Miyata, M.; Ikuta, K.; Hasegawa, Y.; Oneyama, C.; Kanda, T. Efficient Epstein-Barr Virus Progeny Production Mediated by Cancer-Derived LMP1 and Virally-Encoded microRNAs. Microorganisms 2019, 7, 119.

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