School of Molecular and Cellular Biology and Astbury Centre of Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Cancers (Basel). 2014 Jun 27;6(3):1267-97. doi: 10.3390/cancers6031267.
A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC.
全球五分之一的癌症病例具有感染性起源,其中病毒感染是首要原因。一种这样的癌症是 Merkel 细胞癌(MCC),这是一种罕见但具有侵袭性的皮肤恶性肿瘤。2008 年,Merkel 细胞多瘤病毒(MCPyV)被发现是 MCC 的致病因子。它以克隆整合的方式存在于大多数 MCC 肿瘤中,这些肿瘤需要 MCPyV 致癌蛋白才能存活。自发现以来,研究开始揭示 MCPyV 的分子病毒学,以及它如何诱导肿瘤发生。它被认为是一种常见的皮肤共生菌,在健康个体中以低水平存在。当免疫监视丧失时,MCPyV 重新激活,大量病毒载量与 MCC 发病机制相关。尽管 MCPyV 在许多方面与经典致癌性多瘤病毒(如 SV40)相似,但细微的差异开始显现。这些独特的特征突出了 MCPyV 作为唯一的人类致癌性多瘤病毒的独特地位,并为针对 MCC 的治疗开辟了新的途径。