Characterization of beta papillomavirus E4 expression in tumours from Epidermodysplasia Verruciformis patients and in experimental models
Characterization of beta papillomavirus E4 expression in tumours from Epidermodysplasia Verruciformis patients and in experimental models
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DOI：
10.1016/j.virol.2011.11.029
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发表时间：
2012-02-20
期刊：
影响因子：
3.7
通讯作者：
Gariglio, Marisa
中科院分区：
文献类型：
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作者：
Borgogna, Cinzia;Zavattaro, Elisa;Gariglio, Marisa
这项研究提供了EV患者（β-HPV诱导的皮肤癌的人类模型）肿瘤中生命周期事件的第一个特征，并显示了E4表达模式的变化与疾病严重程度的关系。β-HPV生命周期也已经在使用EV衍生的角质形成细胞产生的器官型筏培养物中重建。在EV病变和筏培养物中，在分化细胞中检测到丰富的细胞质E4表达，沿着病毒基因组扩增，如对其他HPV类型所报告的。E4表达也见于某些EV皮肤癌的PCNA阳性基底细胞以及HPV 8 CER（完全早期区）转基因小鼠的肿瘤中。在这些病变中，E4染色延伸到整个上皮厚度，并在明显的非典型细胞中明显。肿瘤边缘这种染色的丧失表明存在一种不同类型的E4失调，可以将其用作β-HPV相关皮肤癌进展期间病毒表达的标志物。(C)2011 Elsevier Inc. All rights reserved.
This study provides a first characterisation of life-cycle events in tumours abscised from EV patients (the human model of beta-HPV-induced skin cancer), and shows how changes in E4 expression patterns relate to disease severity. beta-HPV life-cycle has also been reconstructed in organotypic raft cultures created using EV-derived keratinocytes. In EV lesions and raft cultures, abundant cytoplasmic E4 expression was detectable in differentiating cells along with viral genome amplification as reported for other HPV types. E4 expression was also seen in PCNA-positive basal cells in some EV skin cancers as well as in tumours from HPV8CER (Complete Early Region) transgenic mice. In these lesions, E4 staining extended throughout the full thickness of the epithelium and was apparent in the markedly atypical cells. The loss of such staining at the tumour border suggests a distinct type of E4 dysregulation that may be exploited as a marker of viral expression during beta-HPV-associated skin cancer progression. (C) 2011 Elsevier Inc. All rights reserved.