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Regulation of host and viral promoters during human cytomegalovirus latency via US28 and CTCF
Journal of General Virology ( IF 3.8 ) Pub Date : 2021-05-27 , DOI: 10.1099/jgv.0.001609
Elizabeth G Elder 1, 2 , Benjamin A Krishna 2 , Emma Poole 2 , Marianne Perera 2 , John Sinclair 2
Affiliation  

Viral latency is an active process during which the host cell environment is optimized for latent carriage and reactivation. This requires control of both viral and host gene promoters and enhancers often at the level of chromatin, and several viruses co-opt the chromatin organiser CTCF to control gene expression during latency. While CTCF has a role in the latencies of alpha- and gamma-herpesviruses, it was not known whether CTCF played a role in the latency of the beta-herpesvirus human cytomegalovirus (HCMV). Here, we show that HCMV latency is associated with increased CTCF expression and CTCF binding to the viral major lytic promoter, the major immediate early promoter (MIEP). This increase in CTCF binding is dependent on the virally encoded G protein coupled receptor, US28, and contributes to suppression of MIEP-driven transcription, a hallmark of latency. Furthermore, we show that latency-associated upregulation of CTCF represses expression of the neutrophil chemoattractants S100A8 and S100A9 which we have previously shown are downregulated during HCMV latency. As with downregulation of the MIEP, CTCF binding to the enhancer region of S100A8/A9 drives their suppression, again in a US28-dependent manner. Taken together, we identify CTCF upregulation as an important mechanism for optimizing latent carriage of HCMV at both the levels of viral and cellular gene expression.

中文翻译:

通过 US28 和 CTCF 在人类巨细胞病毒潜伏期中调节宿主和病毒启动子

病毒潜伏期是一个主动过程,在此过程中宿主细胞环境针对潜伏携带和重新激活进行了优化。这需要在染色质水平控制病毒和宿主基因启动子和增强子,并且一些病毒选择染色质组织者 CTCF 来控制潜伏期的基因表达。虽然 CTCF 在 α 和 γ 疱疹病毒的潜伏期中起作用,但尚不清楚 CTCF 是否在 β 疱疹病毒人类巨细胞病毒 (HCMV) 的潜伏期中起作用。在这里,我们显示 HCMV 潜伏期与 CTCF 表达增加和 CTCF 与病毒主要裂解启动子(主要立即早期启动子 (MIEP))结合有关。CTCF 结合的这种增加依赖于病毒编码的 G 蛋白偶联受体 US28,并有助于抑制 MIEP 驱动的转录,延迟的标志。此外,我们表明,与潜伏期相关的 CTCF 上调抑制了中性粒细胞趋化因子 S100A8 和 S100A9 的表达,我们之前已证明在 HCMV 潜伏期期间下调。与 MIEP 的下调一样,CTCF 与 S100A8/A9 的增强子区域的结合驱动它们的抑制,再次以 US28 依赖的方式。总之,我们将 CTCF 上调确定为在病毒和细胞基因表达水平上优化 HCMV 潜伏携带的重要机制。CTCF 与 S100A8/A9 的增强子区域结合驱动它们的抑制,再次以 US28 依赖的方式。总之,我们将 CTCF 上调确定为在病毒和细胞基因表达水平上优化 HCMV 潜伏携带的重要机制。CTCF 与 S100A8/A9 的增强子区域结合驱动它们的抑制,再次以 US28 依赖的方式。总之,我们将 CTCF 上调确定为在病毒和细胞基因表达水平上优化 HCMV 潜伏携带的重要机制。
更新日期:2021-05-28
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