Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
Virology. 2013 Jan 5;435(1):118-30. doi: 10.1016/j.virol.2012.09.029.
A marked escalation in the rate of discovery of new types of human polyomavirus has occurred over the last five years largely owing to recent technological advances in their detection. Among the newly discovered viruses, Merkel Cell Polyomavirus (MCPyV or MCV) has gained the most attention due to its link with a rare human cancer. Infection with MCPyV is common in the human population, and the virus is detected in several anatomical locations, but most frequently in skin. Study of MCPyV molecular virology has been complicated by the lack of straightforward cell culture models, but recent in vitro studies are making strides towards understanding the virus life cycle, its cellular tropism, and mode of transmission. While MCPyV shares several traditional traits with other human polyomaviruses, the burst of research since its discovery reveals insight into a virus with many unique genetic and mechanistic features. The evidence for a causal link between MCPyV and the rare neuroendocrine cancer, Merkel Cell Carcinoma (MCC), is compelling. A majority of MCCs contain clonally integrated viral DNA, express viral T antigen transcripts and protein, and exhibit an addiction to the viral large T and small t antigen oncoproteins. The MCPyV large T antigen contains MCC tumor-specific mutations that ablate its replication capacity but preserve its oncogenic functions, and the small t antigen promotes an environment favorable for cap-dependent translation. The mechanisms of MCPyV-induced transformation have not been fully elucidated, but the likely etiological role of this new polyomavirus in human cancer provides a strong opportunity to expand knowledge of virus-host interactions and viral oncology.
在过去五年中，由于新型人类多瘤病毒检测技术的最新进展，新型人类多瘤病毒的发现率显著上升。在新发现的病毒中，默克尔细胞多瘤病毒（Merkel Cell Polyomavirus，MCPyV 或 MCV）因其与罕见人类癌症的关联而受到最多关注。人类人群中普遍存在感染 MCPyV 的情况，该病毒存在于多个解剖部位，但最常见于皮肤。由于缺乏直接的细胞培养模型，对 MCPyV 分子病毒学的研究变得复杂，但最近的体外研究正在朝着理解病毒生命周期、细胞嗜性和传播模式的方向取得进展。虽然 MCPyV 与其他人类多瘤病毒具有一些传统特征，但自发现以来的大量研究揭示了一种具有许多独特遗传和机制特征的病毒。MCPyV 与罕见神经内分泌癌默克尔细胞癌（Merkel Cell Carcinoma，MCC）之间存在因果关系的证据令人信服。大多数 MCC 中含有克隆整合的病毒 DNA，表达病毒 T 抗原转录本和蛋白，并表现出对病毒大 T 和小 t 抗原致癌蛋白的依赖性。MCPyV 大 T 抗原含有 MCC 肿瘤特异性突变，可消除其复制能力，但保留其致癌功能，而小 t 抗原则促进有利于帽依赖性翻译的环境。MCPyV 诱导转化的机制尚未完全阐明，但这种新型多瘤病毒在人类癌症中的可能病因作用为扩展病毒-宿主相互作用和病毒肿瘤学的知识提供了一个强有力的机会。
