Varicella-zoster virus modulates NF-κB recruitment on selected cellular promoters
Varicella-zoster virus modulates NF-κB recruitment on selected cellular promoters
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DOI：
10.1128/jvi.01378-07
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发表时间：
2007-12-01
影响因子：
5.4
通讯作者：
Sadzot-Delvaux, Catherine
中科院分区：
文献类型：
--
作者：
El Mjiyad, Nadia;Bontems, Sebastien;Sadzot-Delvaux, Catherine
尽管存在促炎细胞因子，例如γ干扰素和肿瘤坏死因子α（TNF-α），但皮肤水痘病变中心的细胞间粘附分子1（ICAM-1）表达下调。为了研究这种下调的分子基础，在水痘带状疱疹病毒（VZV）感染的黑色素瘤细胞（MeWo）中分析了 ICAM-1 对 TNF-α 的诱导，得出以下观察结果：（i）VZV 抑制 icam-1 mRNA 合成的刺激； (ii) 尽管 VZV 诱导 p65、p52 和 c-Rel 发生核易位，但 p50 不会响应 TNF-α 发生易位； (iii) VZV感染细胞中存在的核p65不再与p50相关，并且不能结合icam-1启动子的近端NF-κB位点，尽管启动子响应TNF-α而乙酰化和可及性增加； (iv) VZV 诱导 NF-κ B 抑制剂 p100 的核积累。 VZV 还通过强烈减少 MRC5 成纤维细胞中的 NF-kappa B 核转位来抑制 TNF-a 的 icam-1 刺激。总而言之，这些数据表明 VZV 通过抑制 NF-κ B 结合和靶基因的表达来干扰免疫反应的多个方面。 NF-kappa B 激活在先天性和适应性免疫反应中发挥着核心作用，靶向 NF-kappa B 激活可以为病毒带来明显的优势，特别是在黑素细胞中，黑素细胞是病毒在皮肤中复制的部位。
Intercellular adhesion molecule 1 (ICAM-1) expression is down-regulated in the center of cutaneous varicella lesions despite the expression of proinflammatory cytokines such as gamma interferon and tumor necrosis factor alpha (TNF-alpha). To study the molecular basis of this down-regulation, the ICAM-1 induction of TNF-alpha was analyzed in varicella-zoster virus (VZV)-infected melanoma cells (MeWo), leading to the following observations: (i) VZV inhibits the stimulation of icam-1 mRNA synthesis; (ii) despite VZV-induced nuclear translocation of p65, p52, and c-Rel, p50 does not translocate in response to TNF-alpha; (iii) the nuclear p65 present in VZV-infected cells is no longer associated with p50 and is unable to bind the proximal NF-kappa B site of the icam-1 promoter, despite an increased acetylation and accessibility of the promoter in response to TNF-alpha; and (iv) VZV induces the nuclear accumulation of the NF-kappa B inhibitor p100. VZV also inhibits icam-1 stimulation of TNF-a by strongly reducing NF-kappa B nuclear translocation in MRC5 fibroblasts. Taken together, these data show that VZV interferes with several aspects of the immune response by inhibiting NF-kappa B binding and the expression of target genes. Targeting NF-kappa B activation, which plays a central role in innate and adaptive immune responses, leads to obvious advantages for the virus, particularly in melanocytes, which are a site of viral replication in the skin.