Merkel Cell Polyomavirus Small T Antigen mRNA Level Is Increased following In Vivo UV-Radiation
Merkel Cell Polyomavirus Small T Antigen mRNA Level Is Increased following In Vivo UV-Radiation
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DOI：
10.1371/journal.pone.0011423
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发表时间：
2010-07-02
期刊：
影响因子：
3.7
通讯作者：
Galibert, Marie-Dominique
中科院分区：
文献类型：
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作者：
Mogha, Ariane;Fautrel, Alain;Galibert, Marie-Dominique
默克尔细胞癌 (MCC) 是一种罕见但侵袭性的皮肤癌，涉及默克尔细胞。最近，一种新的人类多瘤病毒与 MCC 相关，它存在于 80% 的分析样本中。在病毒阳性 MCC 中，默克尔细胞多瘤病毒 (MCPyV) 克隆整合到患者 DNA 中，并在其大 T 抗原中携带突变，导致蛋白质被截短。在无症状组织中，MCPyV 的水平非常低。 MCC 还与年龄较大、免疫抑制和日晒有关。然而，与日光照射之间的联系仍然未知，因为 MCPyV 感染时间和 MCC 发展之间涉及的精确机制和步骤。因此，我们研究了太阳模拟辐射（SSR）对 MCPyV 转录活性的潜在影响。我们筛选了 20 名健康患者的皮肤样本，这些患者参加了基于体内施用 2 和 4 J/cm(2) SSR 的光皮肤病学方案。两名患者感染了 MCPyV 的两种新变种，以游离形式存在，对 SSR 照射的皮肤样本进行 RT-QPCR 分析显示 MCPyV 小 t 抗原转录物出现特异性且独特的剂量依赖性增加。基于荧光素酶的体外测定证实小 t 启动子确实是紫外线诱导的。这些发现表明太阳辐射对 MCPyV mRNA 水平有影响，这可以解释 MCC 与太阳照射之间的关联。
Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer involving Merkel cells. Recently, a new human polyomavirus was implicated in MCC, being present in 80% of the samples analyzed. In virus-positive MCC, the Merkel cell polyomavirus (MCPyV) is clonally integrated into the patients DNA, and carries mutations in its large T antigen, leading to a truncated protein. In non-symptomatic tissue MCPyV can reside at very low levels. MCC is also associated with older age, immunosuppression and sun exposure. However, the link with solar exposure remains unknown, as the precise mechanism and steps involved between time of infection by MCPyV and the development of MCC. We thus investigated the potential impact of solar simulated radiation (SSR) on MCPyV transcriptional activity. We screened skin samples of 20 healthy patients enrolled in a photodermatological protocol based on in vivo-administered 2 and 4 J/cm(2) SSR. Two patients were infected with two new variants of MCPyV, present in their episomal form and RT-QPCR analyses on SSR-irradiated skin samples showed a specific and unique dose-dependent increase of MCPyV small t antigen transcript. A luciferase based in vitro assay confirmed that small t promoter is indeed UV-inducible. These findings demonstrate that solar radiation has an impact on MCPyV mRNA levels that may explain the association between MCC and solar exposure.