Effects of varicella-zoster virus on cell cycle regulatory pathways.
Effects of varicella-zoster virus on cell cycle regulatory pathways.
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水痘带状疱疹病毒对细胞周期调控途径的影响。
DOI：
10.1007/82_2010_28
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发表时间：
2010
影响因子：
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通讯作者：
Greenblatt,RebeccaJ
中科院分区：
文献类型：
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作者：
Moffat,JenniferF;Greenblatt,RebeccaJ
水痘-带状疱疹病毒(VZV)在静止期、活体细胞和培养细胞中高效生长，病毒感染激活细胞周期和信号通路，而不是细胞分裂。在SCID-HU小鼠模型中，VZV ORF已被确定为决定未分裂皮肤、T细胞和神经元的组织嗜性。人包皮成纤维细胞具有正常的细胞周期状态，感染VZV后细胞周期状态处于失调状态。细胞周期蛋白A、B1和D3的表达显著升高，但与细胞内广泛的DNA合成不一致。细胞周期停滞可能是由于VZV DNA复制过程中DNA损伤反应的激活所致。在感染的细胞中还诱导了其他宿主调节蛋白，包括p27、p53和ATM激酶。细胞周期调节蛋白增加的一个可能解释是VZV感染过程中转录因子的激活。有证据表明，VZV感染通过有丝分裂原激活的蛋白激酶途径细胞外调节激酶(ERK)和c-Jun氨基末端(转座复合名词的这些部分)激酶(JNK)激活转录因子，从而选择性地提高细胞周期蛋白水平。其中一些受干扰的细胞功能对VZV的复制至关重要，例如细胞周期蛋白依赖性激酶(CDK)的活性，并揭示了干预的目标。
Varicella-zoster virus (VZV) grows efficiently in quiescent cellsin vivoand in culture, and virus infection activates cell cycle and signaling pathways without cell division. VZV ORFs have been identified that determine the tissue tropism for nondividing skin, T cells, and neurons in SCID-Hu mouse models. The normal cell cycle status of human foreskin fibroblasts was characterized and was dysregulated upon infection by VZV. The expression of cyclins A, B1, and D3 was highly elevated but did not correspond with extensive cellular DNA synthesis. Cell cycle arrest may be due to activation of the DNA damage response during VZV DNA replication. Other host regulatory proteins were induced in infected cells, including p27, p53, and ATM kinase. A possible explanation for the increase in cell cycle regulatory proteins is activation of transcription factors during VZV infection. There is evidence that VZV infection activates transcription factors through the mitogen-activated protein kinase pathways extracellular-regulated kinase (ERK) and c-Jun N-terminal (transpose these parts of the compound noun) kinase (JNK), which could selectively increase cyclin levels. Some of these perturbed cell functions are essential for VZV replication, such as cyclin-dependent kinase (CDK) activity, and reveal targets for interventions.