Activation of NF-κB by the latent vFLIP gene of Kaposi's sarcoma-associated herpesvirus is required for the spindle shape of virus-infected endothelial cells and contributes to their proinflammatory phenotype
Activation of NF-κB by the latent vFLIP gene of Kaposi's sarcoma-associated herpesvirus is required for the spindle shape of virus-infected endothelial cells and contributes to their proinflammatory phenotype
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DOI：
10.1128/jvi.01603-05
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发表时间：
2006-07-01
影响因子：
5.4
通讯作者：
Ganem, Don
中科院分区：
文献类型：
--
作者：
Grossmann, Claudia;Podgrabinska, Simona;Ganem, Don
卡波西肉瘤（KS）是一种由KS相关疱疹病毒（KSHV）感染内皮细胞引起的炎性血管增生性病变。感染的内皮细胞呈细长（梭形）形状，这是KS的组织学特征之一。在体外，潜伏的病毒感染的原代内皮细胞（但没有其他类型的细胞）惊人地概括了这些形态学的研究结果。在这里，我们报告的纺锤形表型涉及肌动蛋白细胞骨架的主要重排，可以归因于一个单一的病毒蛋白，vFLIP，一个已知的NF-κ B的激活剂的表达。与此一致，NF-κ B活化的抑制阻断了培养的内皮细胞中vFLIP诱导的纺锤形。梭形细胞中的vFLIP表达还诱导多种促炎性细胞因子和细胞表面粘附蛋白的产生，这些细胞因子和细胞表面粘附蛋白可能有助于KS病变的炎性组分。
Kaposi's sarcoma (KS) is an inflammatory angioproliferative lesion induced by the infection of endothelial cells with the KS-associated herpesvirus (KSHV). Infected endothelial cells assume an elongated (spindle) shape that is one of the histologic signatures of KS. In vitro, latent viral infection of primary endothelial cells (but no other cell type) strikingly recapitulates these morphological findings. Here we report that the spindling phenotype involves major rearrangement of the actin cytoskeleton and can be attributed to the expression of a single viral protein, vFLIP, a known activator of NF-kappa B. Consistent with this, the inhibition of NF-kappa B activation blocks vFLIP-induced spindling in cultured endothelial cells. vFLIP expression in spindle cells also induces the production of a variety of proinflammatory cytokines and cell surface adhesion proteins that likely contribute to the inflammatory component of KS lesions.