Epstein-Barr virus (EBV)-Encoded RNA 2 (EBER2) but not EBER1 plays a critical role in EBV-Induced B-Cell growth transformation

Epstein-Barr virus (EBV)-Encoded RNA 2 (EBER2) but not EBER1 plays a critical role in EBV-Induced B-Cell growth transformation
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DOI:
10.1128/jvi.00579-07
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发表时间:
2007-10-01
影响因子:
5.4
通讯作者:
Takada, Kenzo
Takada, Kenzo
中科院分区:
医学2区
文献类型:
--
作者:
Wu, Yi;Maruo, Seiji;Takada, Kenzo

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EB病毒(EB病毒)编码的RNA 1(EBER 1)和EBER 2是非翻译RNA,也是潜伏性EB病毒感染细胞中最丰富的病毒转录本。我们先前报道EBER在EBV诱导的原代B细胞生长转化中起关键作用。为了研究EBER 1和EBER 2在B细胞生长转化中是否具有不同的作用,产生了携带EBER 1或EBER 2的重组EBV。表达EBER 2的重组EBV的转化能力与同时表达EBER 1和EBER 2的EBV的转化能力一样高。相反,携带EBER 1的重组EBV的转化能力受损,并且与缺乏EBER 1和EBER 2的EBV的转化能力相似。用携带EBER 2的EBV建立的淋巴母细胞样细胞系(LCL)在低细胞密度下增殖,而用携带EBER 1的EBV建立的LCL则没有。表达EBER 2的LCL中白细胞介素6(IL-6)的产生比缺乏EBER 2的LCL中更丰富。缺乏EBER 2的LCL的生长通过向细胞培养物中添加重组IL-6而增强,而表达EBER 2的LCL的生长通过中和抗IL-6抗体而抑制。这些结果表明,EBER 2,而不是EBER 1,有助于有效的B细胞生长转化。我们得出结论,EBER 1和EBER 2,尽管它们的结构相似,在潜伏感染的淋巴母细胞有不同的功能。
Epstein-Barr virus (EBV)-encoded RNA 1 (EBER1) and EBER2 are untranslated RNAs and the most abundant viral transcripts in latently EBV-infected cells. We previously reported that EBERs play a critical role in efficient EBV-induced growth transformation of primary B cells. To investigate whether EBER1 and EBER2 have distinct roles in B-cell growth transformation, recombinant EBVs carrying either EBER1 or EBER2 were generated. The transforming ability of recombinant EBVs expressing EBER2 was as high as that of EBVs expressing both EBER1 and EBER2. In contrast, the transforming ability of recombinant EBVs carrying EBER1 was impaired and was similar to that of EBV lacking both EBER1 and EBER2. Lymphoblastoid cell lines (LCLs) established with EBVs carrying EBER2 proliferated at low cell densities, while LCLs established with EBVs carrying EBER1 did not. Interleukin 6 (IL-6) production in LCLs expressing EBER2 was more abundant than in those lacking EBER2. The growth of LCLs lacking EBER2 was enhanced by the addition of recombinant IL-6 to the cell culture, while the growth of EBER2-expressing LCLs was inhibited by a neutralizing anti-IL-6 antibody. These results demonstrate that EBER2, but not EBER1, contributes to efficient B-cell growth transformation. We conclude that EBER1 and EBER2, despite their structural similarity, have different functions in latently infected lymphoblastoid cells.