论文部分内容阅读
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。
OBJECTIVE: To summarize the structure and function of polyoma virus genes, and to further analyze the research progress of polyomavirus T antigen in transgenic animal models. Methods: The PubMed database search system was used to search the related literature of 1990-2011 with the keywords of “SV40virus, simian virus40, JC virus, John Cunningham virus and BK virus”. A total of 23 254 English articles were retrieved. Inclusion criteria: 1) the structural features of the polyoma virus genome; 2) the biological function of polyoma virus-encoded products; and 3) the progress of polyoma virus in transgenic animal models. According to the inclusion criteria, 40 important articles were analyzed. Results: The polyoma virus is a small, circular, closed, double-stranded, approximately 5 000 bp DNA virus that includes three major functional domains: the early coding region, the late coding region, and the non-coding region. The early coding region forms a large T antigen and a small t antigen through alternative splicing. The large T antigen is involved in the replication and transcriptional regulation of early and late DNA and is inactivated after binding with the tumor suppressor genes Rb and p53, and then inactivates with various malignancies Tumor is closely related. Although the sequence homology of SV40 and JC virus T antigen is very high, most SV40T antigen transgenic animals can show tumors, whereas JC virus T antigen mostly induces nervous system tumors. The occurrence of tumors is mainly caused by the correctness of virus T antigen After the expression of the complete existence of the decision. Conclusion: The establishment of malignant epithelial tumor transgenic mice using polyomavirus T antigen not only confirms its relationship with malignant epithelial tumors, but also provides an important means to reveal its carcinogenic mechanism and gene therapy of epithelial tumors.