vFLIP from KSHV inhibits anoikis of primary endothelial cells
vFLIP from KSHV inhibits anoikis of primary endothelial cells
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DOI：
10.1242/jcs.022343
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发表时间：
2008-02-15
影响因子：
4
通讯作者：
Collins, Mary K.
中科院分区：
文献类型：
--
作者：
Efklidou, Sofia;Bailey, Ranbir;Collins, Mary K.
内皮细胞的卡波西肉瘤相关疱疹病毒（KSHV或HHV-8）感染是内皮细胞肿瘤卡波西肉瘤（KS）病因学的早期事件。我们研究了KSHV潜伏蛋白病毒FLICE样抑制蛋白（vFLIP）对真皮微血管内皮细胞（MVEC）存活的影响，因为vFLIP在KS病变内的KSHV感染细胞中表达。为此，我们使用慢病毒载体在不存在其他KSHV蛋白的情况下在MVEC中表达vFLIP。vFLIP激活MVEC中的经典NF-κ B途径并引起RelA/p65的核转位。这种NF-κ B活化可防止MVEC的失巢凋亡，但不抑制去除包括血管内皮生长因子（VEGF）在内的必需存活因子诱导的凋亡。vFLIP表达部分通过诱导额外的旁分泌存活因子的分泌来抑制失巢凋亡。这些结果对KS发展的影响进行了讨论。
Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) infection of endothelial cells is an early event in the aetiology of the endothelial cell tumour Kaposi's sarcoma (KS). We have examined the effect of the KSHV latent protein viral FLICE-like inhibitory protein (vFLIP) on dermal microvascular endothelial cell (MVEC) survival as vFLIP is expressed in the KSHV-infected cells within KS lesions. To do this, we have used a lentiviral vector to express vFLIP in MVECs in the absence of other KSHV proteins. vFLIP activates the classical NF-kappa B pathway in MVECs and causes nuclear translocation of RelA/p65. This NF-kappa B activation prevents detachment-induced apoptosis (anoikis) of MVECs but does not inhibit apoptosis induced by removal of essential survival factors, including vascular endothelial growth factor (VEGF). vFLIP expression inhibits anoikis in part by inducing the secretion of an additional paracrine survival factor(s). The implications of these results for KS development are discussed.