Epstein-Barr virus-induced epigenetic alterations following transient infection.
Epstein-Barr virus-induced epigenetic alterations following transient infection.
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DOI：
10.1002/ijc.27893
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发表时间：
2013-05-01
影响因子：
6.4
通讯作者：
Scott, Rona S.
中科院分区：
文献类型：
--
作者：
Queen, Krista J.;Shi, Mingxia;Zhang, Fangfang;Cvek, Urska;Scott, Rona S.
EB 病毒 (EBV) 是一种已知的肿瘤病毒，与越来越多的恶性肿瘤相关。然而，该病毒与某些恶性肿瘤的关联常常不稳定。为了确定 EBV 在不完全关联的情况下对肿瘤发生的贡献，建立了瞬时感染模型，其中感染重组 EBV 的克隆 CCL185 癌细胞系通过撤消选择压力而失去病毒基因组。将 EBV 阴性、短暂感染的克隆与未感染的对照进行比较，发现了 1000 多个基因的表达变化。在下调基因中，发现了一些已知在癌症中 DNA 甲基化的基因，包括 E-钙粘蛋白和 PYCARD。 EBV 阳性细胞中存在的钙粘蛋白开关、运动性增加和细胞侵袭性增强在病毒丢失后得以保留，表明存在表观遗传效应。 PYCARD 表达的抑制是由于启动子 CpG 甲基化增加所致，而短暂 EBV 感染后 E-钙粘蛋白表达的丧失与 E-钙粘蛋白启动子 DNA 甲基化增加无关。相反，E-钙粘蛋白的抑制与抑制染色质状态的形成是一致的。相对于未感染的对照，在 EBV 阴性、瞬时感染的克隆中观察到 E-钙粘蛋白基因启动子和 5' 末端的组蛋白 3 或 4 乙酰化减少。这些结果表明，EBV 可以在先前感染的细胞中以可遗传的方式稳定地改变基因表达，而其自身对致癌过程的贡献被掩盖。
Epstein-Barr virus (EBV) is a known tumor virus associated with an increasing array of malignancies; however, the association of the virus with certain malignancies is often erratic. To determine EBV’s contributions to tumorigenesis in a setting of incomplete association, a transient model of infection was established where a clonal CCL185 carcinoma cell line infected with recombinant EBV was allowed to lose viral genomes by withdrawal of selection pressure. Global gene expression comparing EBV-negative, transiently infected clones to uninfected controls identified expression changes in over 1000 genes. Among downregulated genes, several genes known to be DNA methylated in cancer were identified including E-cadherin and PYCARD. A cadherin switch, increased motility and enhanced cellular invasiveness present in EBV-positive cells were retained following viral loss indicating an epigenetic effect. Repression of PYCARD expression was due to increased promoter CpG methylation, whereas loss of E-cadherin expression after transient EBV infection did not correlate with increased DNA methylation of the E-cadherin promoter. Rather, repression of E-cadherin was consistent with formation of a repressive chromatin state. Decreased histone 3 or 4 acetylation at the promoter and 5’ end of the E-cadherin gene was observed in an EBV-negative, transiently infected clone relative to the uninfected controls. These results suggest that EBV can stably alter gene expression in a heritable fashion in formerly infected cells, while its own contribution to the oncogenic process is masked.
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影响因子：
14.9
作者：
Ongenaert M;Van Neste L;De Meyer T;Menschaert G;Bekaert S;Van Criekinge W
通讯作者：
Van Criekinge W
影响因子：
50.5
作者：
Nerurkar, AY;Vijayan, P;Naresh, KN
通讯作者：
Naresh, KN
影响因子：
5.4
作者：
Ellis, Amy L.;Wang, Zhenxun;Mertz, Janet E.
通讯作者：
Mertz, Janet E.
影响因子：
7.7
作者：
Gruffat, H;Manet, E;Sergeant, A
通讯作者：
Sergeant, A
DOI：
10.1099/vir.0.007922-0
发表时间：
2009-06
期刊：
The Journal of general virology
影响因子：
--
作者：
Heather J;Flower K;Isaac S;Sinclair AJ
通讯作者：
Sinclair AJ