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

Microorganisms

Yasuhisa Hasegawa¹  Chitose Oneyama²  Mamiko Miyata²  Kazufumi Ikuta³  Teru Kanda³  Misako Yajima³ 

[1] Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan;Division of Cancer Cell Regulation, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan;Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan;

关键词: Epstein-Barr virus;    Nasopharyngeal carcinoma;    LMP1;    BART;    microRNA;   

DOI  :  10.3390/microorganisms7050119

来源: DOAJ

【 摘 要 】

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 (LMP1_CAO) or LMP1 from a prototype B95-8 strain of EBV (LMP1_B95-8). When an EBV-BAC clone DNA encoding LMP1_CAO was stably transfected into HEK293 cells, it generated many more stable transformants than the control clone encoding LMP1_B95-8. 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.

【 授权许可】

Unknown