The copy number of Epstein-Barr virus latent genome correlates with the oncogenicity by the activation level of LMP1 and NF-κB.
The copy number of Epstein-Barr virus latent genome correlates with the oncogenicity by the activation level of LMP1 and NF-κB.
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Epstein-Barr 病毒潜在基因组的拷贝数与 LMP1 和 NF-κB 激活水平的致癌性相关
DOI：
10.18632/oncotarget.5708
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Lu J
中科院分区：
文献类型：
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作者：
Zuo L;Yu H;Liu L;Tang Y;Wu H;Yang J;Zhu M;Du S;Zhao L;Cao L;Li G;Lu J
利用Maxi-EBV系统建立了EB病毒（Epstein-Barr virus，EBV）潜伏感染促进致瘤性的肿瘤模型。在本方法中，EBV丢失的细胞克隆表现出显著降低的肿瘤发生。另一方面，Maxi-EBV基因组中的LMP 1基因被鼻咽癌来源的LMP 1基因取代。所得细胞系293-1/NL显示出比原始293-EBV低得多的恶性度。结果与我们的期望相反。293个亚系细胞的EBV携带变化也得到了类似的结果。为探讨其原因，检测了所有细胞系中EBV基因组的拷贝数。结果表明，293-EBV的拷贝数是293-1/NL的4.5倍。平行的EBV基因组在不同的293个亚系中产生相对稳定的拷贝，这表明病毒基因组结构是EBV拷贝数可持续性的一个因素。此外，在高拷贝的细胞中，LMP 1的转录显示出异常高的水平。此外，主要的LMP 1驱动的途径，转录因子NF-κB，在高拷贝细胞中高度活化。本研究首次通过实验模型证实了EB病毒潜伏基因组拷贝数与病毒致病机制的相关性，其依赖于LMP 1和NF-κB的活化水平。总体而言，EBV基因组的存在和数量对于病毒致瘤性至关重要。
A tumor model that Epstein-Barr virus (EBV) latent infection facilitated the tumorigenicity was previously established using the Maxi-EBV system. In the present approach, EBV-lost cell clones demonstrated significantly decreased tumorigenesis. On the other hand, the LMP1 gene in Maxi-EBV genome was replaced by that of nasopharyngeal carcinoma origin. The resultant cell line, 293–1/NL showed much lower malignancy than the original 293-EBV. The result was opposite to our expectation. The change of 293 sublineage cells for EBV harboring also got similar result. To seek the underlying reason, the copy number of EBV genome in all the cell lines was detected. The result indicated that 293-EBV contained about 4.5-fold higher EBV copies than 293–1/NL did. Parallel EBV genomes led to relatively stable copies in different 293 sublineages, suggesting the viral genome structure is a factor for the sustainability of EBV's copy number. Moreover, the LMP1 transcription in high copy-containing cells showed abnormally high level. Furthermore, the main LMP1-driven pathway, transcription factor NF-κB, was highly activated in high-copy cells. Here we first manifest by experimental model that the copy number of EBV latent genome correlates with the viral pathogenesis, which depends on the activation level of LMP1 and NF-κB. Overall, both the presence and amount of EBV genome are crucial for the viral oncogenicity.