Matsushita Michiko, Iwasaki Takeshi, Kuwamoto Satoshi, Kato Masako, Nagata Keiko, Murakami Ichiro, Kitamura Yukisato, Hayashi Kazuhiko
Division of Molecular Pathology, Department of Pathology, Tottori University Faculty of Medicine, Nishi-cho 86, Yonago, Tottori, 683-8503, Japan,
Virus Genes. 2014 Apr;48(2):233-42. doi: 10.1007/s11262-013-1023-y. Epub 2013 Dec 19.
Most of merkel cell carcinomas (MCC), a rare, aggressive skin cancer with neuroendocrine features, harbor merkel cell polyomavirus (MCPyV). Seroepidemiological studies suggested high prevalence of MCPyV in the human population. More than ten sequence data on MCPyV strains in Japan have been available, whereas most sequence data were detected from patients living in Europe or European ancestry. Analysis of nine almost complete and 19 partial sequences from two oncogenes, small T antigen (ST) and large T antigen (LT) genomes obtained from 32 Japanese MCPyV-infected MCC revealed that each Japanese MCPyV-infected MCC harbored a specific MCPyV strain with some synonymous or, silent mutations and stop codons or deletions, but functional domains of T antigen had no amino acid changes. All stop codons were localized after retinoblastoma protein-binding domain. These Japanese MCPyV strains were very closely interrelated to themselves and a consensus sequence of Japanese strain was generated. Phylogenetic analysis of our nine sequences and 70 other sequences for ST and LT gene registered in GenBank indicated that Japanese or Asian MCPyV strains formed distinct clades from Caucasian clade, and phylogenetic tree of our nine and 75 other sequences for ST gene formed characteristic three clades and showed that all Japanese or Asian strains were included in the dominant clade. These suggested the possibility of geographically related genotypes of MCPyV. The genomic characterization of MCPyV variants will provide an important database and insights for illuminating their evolutional and biological differences.
默克尔细胞癌(MCC)是一种罕见的、具有神经内分泌特征的侵袭性皮肤癌,大多数病例都携带着默克尔细胞多瘤病毒(MCPyV)。血清流行病学研究表明,MCPyV在人群中的感染率很高。日本已经有十多条关于MCPyV毒株的序列数据,而大多数序列数据是从生活在欧洲或有欧洲血统的患者中检测到的。对从32例日本MCPyV感染的MCC中获得的两个癌基因(小T抗原(ST)和大T抗原(LT)基因组)的9个几乎完整和19个部分序列进行分析后发现,每例日本MCPyV感染的MCC都携带一种特定的MCPyV毒株,存在一些同义突变或沉默突变、终止密码子或缺失,但T抗原的功能域没有氨基酸变化。所有终止密码子都位于视网膜母细胞瘤蛋白结合域之后。这些日本MCPyV毒株彼此之间密切相关,并生成了日本毒株的一致序列。对我们的9个序列以及GenBank中注册的其他70个ST和LT基因序列进行系统发育分析表明,日本或亚洲的MCPyV毒株与白种人的毒株形成了不同的进化枝,我们的9个序列和其他75个ST基因序列的系统发育树形成了特征性的三个进化枝,并且表明所有日本或亚洲毒株都包含在优势进化枝中。这些结果提示了MCPyV存在地理相关基因型的可能性。MCPyV变异体的基因组特征将为阐明其进化和生物学差异提供重要的数据库和见解。