Inactivating a cellular intrinsic immune defense mediated by Daxx is the mechanism through which the human cytomegalovirus pp71 protein stimulates viral immeiate-early gene expression
Inactivating a cellular intrinsic immune defense mediated by Daxx is the mechanism through which the human cytomegalovirus pp71 protein stimulates viral immeiate-early gene expression
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DOI：
10.1128/jvi.80.8.3863-3871.2006
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发表时间：
2006-04-01
影响因子：
5.4
通讯作者：
Kalejta, RF
中科院分区：
文献类型：
--
作者：
Saffert, RT;Kalejta, RF
人巨细胞病毒（HCMV）巧妙地逃避适应性和先天性免疫反应，使感染得以维持并在宿主的生命中周期性地重新激活。在这里，我们表明细胞也具有针对HCW的内在免疫防御，该防御被病毒解除。在HCMV感染的细胞中，早幼粒细胞白血病核小体（PML-NB）蛋白Daxx通过组蛋白脱乙酰酶的作用使病毒立即早期基因表达沉默。然而，这种抗病毒策略被病毒pp 71蛋白有效地中和，所述病毒pp 71蛋白被掺入病毒体中，在感染时被递送至细胞，并介导Daxx的蛋白酶体降解。这项工作证明了pp 71激活HCMV感染细胞中病毒立即早期基因表达的机制。此外，它提供了对PML-NB蛋白如何建立针对DNA病毒的内在免疫防御以及HCMV pp 71如何使这种防御失活的见解。
Human cytomegalovirus (HCMV) masterfully evades adaptive and innate immune responses, allowing infection to be maintained and periodically reactivated for the life of the host. Here we show that cells also possess an intrinsic immune defense against HCW that is disarmed by the virus. In HCMV-infected cells, the promyelocytic leukemia nuclear body (PML-NB) protein Daxx silences viral immediate-early gene expression through the action of a histone deacetylase. However, this antiviral tactic is efficiently neutralized by the viral pp71 protein, which is incorporated into virions, delivered to cells upon infection, and mediates the proteasomal degradation of Daxx. This work demonstrates the mechanism through which pp71 activates viral immediate-early gene expression in HCMV-infected cells. Furthermore, it provides insight into how a PML-NB protein institutes an intrinsic immune defense against a DNA virus and how HCMV pp71 inactivates this defense.