Infected T98G glioblastoma cells support human cytomegalovirus reactivation from latency.

Infected T98G glioblastoma cells support human cytomegalovirus reactivation from latency.
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受感染的 T98G 胶质母细胞瘤细胞支持人巨细胞病毒从潜伏期重新激活

DOI:
10.1016/j.virol.2017.07.023
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发表时间:
2017-10
期刊:
影响因子:
3.7
通讯作者:
Luo MH
Luo MH
中科院分区:
医学3区
文献类型:
--
作者:
Cheng S;Jiang X;Yang B;Wen L;Zhao F;Zeng WB;Liu XJ;Dong X;Sun JY;Ming YZ;Zhu H;Rayner S;Tang Q;Fortunato E;Luo MH

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T98 G细胞已显示支持长期人巨细胞病毒(HCMV)基因组维持而无感染性病毒释放。然而,目前还不清楚这些病毒基因组是否可以被重新激活。为了解决这个问题,使用含有GFP基因的重组HCMV(rHCMV)感染T98 G细胞,并且将不产生感染性病毒的感染细胞命名为T98 G-LrV。经二丁酰cAMP + IBMX(cAMP/IBMX)处理后,T98 G-LrV细胞内出现GFP信号增强、病毒基因组复制、裂解基因表达和感染性病毒释放等一系列现象,表明HCMV在T98 G-LrV细胞内由潜伏状态重新激活。cAMP/IBMX诱导的T98 G-LrV细胞中HCMV再活化的机制与PKA-CREB信号通路有关。这些结果表明,HCMV在T98 G-LrV细胞中是潜伏的,并且可以被重新激活。T98 G-LrV细胞是研究神经细胞中HCMV从潜伏期再激活机制的有效模型。
T98G cells have been shown to support long-term human cytomegalovirus (HCMV) genome maintenance without infectious virus release. However, it remains unclear whether these viral genomes could be reactivated. To address this question, a recombinant HCMV (rHCMV) containing a GFP gene was used to infect T98G cells, and the infected cells absent of infectious virus production were designated T98G-LrV. Upon dibutyryl cAMP plus IBMX (cAMP/IBMX) treatment, a serial of phenomena were observed, including GFP signal increase, viral genome replication, lytic genes expression and infectious viruses release, indicating the reactivation of HCMV in T98G-LrV cells from a latent status. Mechanistically, HCMV reactivation in the T98G-LrV cells induced by cAMP/IBMX was associated with the PKA-CREB signaling pathway. These results demonstrate that HCMV was latent in T98G-LrV cells and could be reactivated. The T98G-LrV cells represent an effective model for investigating the mechanisms of HCMV reactivation from latency in the context of neural cells.
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