Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity.

Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity.
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DOI:
10.1016/j.virol.2015.02.009
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发表时间:
2015-05
期刊:
影响因子:
3.7
通讯作者:
Knipe, David M.
Knipe, David M.
中科院分区:
医学3区
文献类型:
--
作者:
Knipe, David M.

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单纯疱疹病毒(HSV)在上皮细胞中经历裂解性感染,在神经细胞中经历潜伏性感染,并且表观遗传机制在这两种情况下的差异基因表达中起主要作用。疱疹病毒DNA不与组蛋白结合,但在进入细胞后迅速装载异染色质。病毒蛋白促进上皮细胞中表观遗传沉默的逆转,而病毒潜伏相关转录物促进神经元细胞中的额外异染色质。启动外源DNA染色质化的细胞传感器尚未完全确定。IFI16和cGAS对于HSV DNA的先天传感都是必不可少的,新的证据表明它们如何共同作用以启动先天信号传导。IFI16也在HSV DNA的异染色质化中发挥作用,本文将研究IFI16如何整合外源病毒DNA的表观遗传调控和先天感应,以显示这两种反应是如何相关的。
Herpes simplex virus (HSV) undergoes a lytic infection in epithelial cells and a latent infection in neuronal cells, and epigenetic mechanisms play a major role in the differential gene expression under the two conditions. Herpes viron DNA is not associated with histones but is rapidly loaded with heterochromatin upon entry into the cell. Viral proteins promote reversal of the epigenetic silencing in epithelial cells while the viral latency-associated transcript promotes additional heterochromatin in neuronal cells. The cellular sensors that initiate the chromatinization of foreign DNA have not been fully defined. IFI16 and cGAS are both essential for innate sensing of HSV DNA, and new evidence shows how they work together to initiate innate signaling. IFI16 also plays a role in the heterochromatinization of HSV DNA, and this review will examine how IFI16 integrates epigenetic regulation and innate sensing of foreign viral DNA to show how these two responses are related.
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