The E6E7 oncoproteins of cutaneous human papillomavirus type 38 interfere with the interferon pathway
The E6E7 oncoproteins of cutaneous human papillomavirus type 38 interfere with the interferon pathway
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DOI：
10.1016/j.virol.2008.04.036
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发表时间：
2008-08-01
期刊：
影响因子：
3.7
通讯作者：
Campo, M. Saveria
中科院分区：
文献类型：
--
作者：
Cordano, Pablo;Gillan, Victoria;Campo, M. Saveria
非黑色素瘤皮肤癌是高加索人群中最常见的恶性肿瘤。有证据表明，皮肤人类乳头瘤病毒(HPV)的贝塔()属参与了这种疾病。HPV的E6和E7促进细胞转化和抑制免疫反应相关途径的能力在宫颈癌的发生中起着关键作用。HPV-38E6和E7在体外和体内模型中都显示出转化活性，但它们对免疫监测的影响尚不清楚。在这里，我们发现HPV-38E6和E7影响干扰素诱导的MHC-I类分子的上调。这两种病毒蛋白在HaCaT角质形成细胞中的表达导致MHC-I类分子水平的降低。这种下调与MHC I重链、多肽伴侣TAP和STAT-1下游效应器IRF-1的表达减少有关。这些蛋白的下调最终归因于STAT-1表达的抑制。对表达HPV-38E6或E7的细胞的分析表明，这些影响主要是E6表达的结果，尽管不能排除E7的贡献。我们得出结论，HPV-38编码的癌蛋白可能有助于逃避宿主的免疫监视。(C)2008 Elsevier Inc.保留所有权利。
Non-melanoma skin cancer is the most frequent malignancy in Caucasian populations. Evidence suggests the involvement of cutaneous Human Papillomavirus (HPV) of the genus beta () in this disease. The ability of E6 and E7 of mucosal HPV to promote cellular transformation and inhibit immune response-related pathways plays a key role in cervical carcinogenesis. beta HPV-38 E6 and E7 display transforming activities in in vitro and in vivo models, but their impact on immune surveillance is unknown. Here we show that HPV-38 E6 and E7 affect the IFN-incluced up-regulation of MHC class I. Expression of the two viral proteins in HaCaT keratinocytes led to a decrease of MHC I levels. This down-regulation is associated with a reduction of expression of MHC I heavy chain, of the peptide chaperone TAP and of the STAT-1 downstream effector IRF-1. The down-regulation of these proteins is ultimately due to the inhibition of STAT-1 expression. Analysis of cells expressing either HPV-38 E6 or E7 suggests that these effects are primarily the result of E6 expression, although a contribution by E7 cannot be excluded. We conclude that HPV-38 encodes oncoproteins that potentially contribute to the evasion of host immune surveillance. (C) 2008 Elsevier Inc. All rights reserved.