【摘要】 目的:总结多瘤病毒基因结构与功能,深入分析多瘤病毒T抗原在转基因动物模型中的研究进展。方法:应用PubMed数据库检索系统,以"SV40virus、simian virus40、JC virus、John Cunningham virus和BK virus"为关键词,检索1990-2011的相关文献,共检索到英文文献23 254条。纳入标准:1)多瘤病毒的基因组结构特点;2)多瘤病毒编码产物的生物学功能;3)多瘤病毒在转基因动物模型中的研究进展。根据纳入标准,符合分析的重要文献40篇。结果:多瘤病毒是小的环状闭合双链大约5 000bp的DNA病毒,包括早期编码区、晚期编码区和非编码调控区3个主要功能区。早期编码区通过选择性剪接形成大T抗原和小t抗原,大T抗原参与早晚期DNA的复制和转录调控,并与抑癌基因Rb和p53蛋白结合后使其失活,进而与多种恶性肿瘤发生关系密切。虽然SV40和JC病毒T抗原的序列同源性极高,但是大多数SV40T抗原转基因动物均可出现肿瘤,而JC病毒T抗原大多诱发出神经系统肿瘤,肿瘤的发生主要是由病毒T抗原的正确表达后完整存在决定的。结论:运用多瘤病毒T抗原建立恶性上皮肿瘤转基因动物研究不但可证实其与恶性上皮肿瘤的关系,也为揭示其致癌机制和上皮肿瘤的基因治疗提供重要手段。更多还原

【Abstract】 OBJECTIVE : To summarize genomic structure and its encoding product ’ s functions of polyoma virus and the establishment of transgenic mice using polyoma oncogenic genes.METHODS : The papers were collected from PubMed database between 1990and 2011according to the key words :" SV40virus " OR " simian virus 40 " OR " JC virus " OR " John Cunningham virus " OR " BK virus "(n=23 254) and selected in terms of the following criteria : 1) The genomic DNA of polyomavirus;2) The biological function of polyomavirus encoding products;3) Transgenic animal models induced by polyomavirus.According to the criteria,40papers were selected.RESULTS : Polyoma viruses have icosahedral caspids and contain small,circular and double-stranded DNA genomes,including early and late coding regions with a regulatory region.The early region is alternatively spliced to produce large T antigen and small t antigen.T antigen can bind to and inactivate such tumor suppressors as p53and pRb,which is closely linked to the tumorigenesis.Although there is high homology between SV40and JCV T antigen,the transgenic mice of SV40Tantigen exhibit various tumors and those of JCV T antigen induce the neural tumors in most cases,which is determined by the correct expression and whole existence of T antigen.CONCLUSIONS : It would be useful to establish transgenic animal of epithelial malignancies using polyoma virus T antigen,which can provide an evidence for its oncogenic role in the carcinogenesis.Additionally,the animal model would become a tool to investigate the molecular mechanisms of JCV oncogenesis and the approach of gene therapy for the cancer.更多还原