BACKGROUND Merkel cell polyomavirus (MCPyV) is a human polyomavirus that establishes a life-long harmless infection in most individuals, with dermal fibroblasts believed to be the natural host cell. However, this virus is the major cause of Merkel cell carcinoma (MCC), an aggressive skin cancer. Several MCPyV variants with polymorphism in their promoter region have been isolated, but it is not known whether these differences affect the biological properties of the virus. METHODS Using transient transfection studies in human dermal fibroblasts and the MCC cell line MCC13, we compared the transcription activity of the early and late promoters of the most commonly described non-coding control region MCPyV variant and six other isolates containing specific mutation patterns. RESULTS Both the early and late promoters were significantly stronger in human dermal fibroblasts compared with MCC13 cells, and a different promoter strength between the MCPyV variants was observed. The expression of full-length large T-antigen, a viral protein that regulates early and late promoter activity, inhibited early and late promoter activities in both cell lines. Nonetheless, a truncated large T-antigen, which is expressed in virus-positive MCCs, stimulated the activity of its cognate promoter. CONCLUSION The promoter activities of all MCPyV variants tested was stronger in human dermal fibroblasts, a cell line that supports viral replication, than in MCC13 cells, which are not permissive for MCPyV. Truncated large T-antigen, but not full-length large T-antigen stimulated viral promoter activity. Whether, the difference in promoter strength and regulation by large T-antigen may affect the replication and tumorigenic properties of the virus remains to be determined.

中文翻译：

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默克尔细胞多瘤病毒变体在人皮肤成纤维细胞和默克尔细胞癌细胞系中的启动子活性。

背景技术默克尔细胞多瘤病毒（MCPyV）是一种人类多瘤病毒，其在大多数个体中建立了终身无害感染，其中真皮成纤维细胞被认为是天然宿主细胞。但是，这种病毒是侵袭性皮肤癌默克尔细胞癌（MCC）的主要原因。已经分离出了在其启动子区域具有多态性的几种MCPyV变体，但尚不清楚这些差异是否影响病毒的生物学特性。方法在人皮肤成纤维细胞和MCC细胞系MCC13中使用瞬时转染研究，我们比较了最常用的非编码控制区MCPyV变体和其他六个含有特定突变模式的分离株的早期和晚期启动子的转录活性。结果与MCC13细胞相比，早期和晚期启动子在人皮肤成纤维细胞中均明显更强，并且在MCPyV变体之间观察到不同的启动子强度。全长大T抗原的表达，一种调节早期和晚期启动子活性的病毒蛋白，在两种细胞系中均抑制早期和晚期启动子活性。但是，在病毒阳性MCC中表达的截短的大T抗原刺激了其同源启动子的活性。结论测试的所有MCPyV变体的启动子活性在人真皮成纤维细胞（一种支持病毒复制的细胞系）中比在MCC13细胞中更强，MCC13细胞不允许MCPyV。截短的大T抗原刺激了病毒启动子活性，但没有全长大T抗原刺激。是否，