摘要
目的:总结JC病毒(JCV)研究现状,深入分析JCV T抗原致癌机制及未来研究方向.方法:应用PubMed数据库检索系统,以“JC virus”或“John Cunningham virus”为关键词,检索1991-01-2012-06的相关文献,共检索到英文文献1599条.纳入标准:1)JCV的基因组结构特点 ;2)JCV编码产物的生物学功能 ;3)JCV与恶性肿瘤发生、发展的关系.根据纳入标准,符合分析的文献41篇.结果:JCV属于多瘤DNA病毒家族成员,基因组早期编码区经选择性剪接编码T抗原和t抗原,晚期编码区编码衣壳蛋白VP1、VP2、VP3及调节蛋白Agno.T抗原可与抑癌基因p53和Rb蛋白结合后导致其失活,使Wnt和IGF信号传导途径发生紊乱,影响基因组稳定性,进而参与肿瘤发生.JCV经静脉、颅内注射及转基因动物实验表明,其可引发各种神经系统肿瘤 ;体内实验结果提示,JCV T抗原DNA存在与消化道、呼吸道肿瘤以及B细胞淋巴瘤关系密切.结论:JCV基因组嵌入后正确表达与恶性肿瘤发生关系密切,运用JCVT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.
Abstract
OBJECTIVE:To summarize the study situation of John Cunningham virus (JCV)and analyze the oncogen-ic role of JCV and future aspect. METHODS: The papers were collected from PubMed database between 1991-01 and 2012-06 according to the key words:"JC virus" OR "John Cunningham virus" (n=l 599) and selected in terms of the following criteria:1) The genomic DNA of JCV; 2) The biological function of JCV encoding products; 3) The relationship between JCV and carcinogenesis(n = 41). RESULTS: JCV is a member of the family of polyoma DNA viruses. The early region of JCV genomic DNA is alternatively spliced to produce large T antigen and small t antigen. The late region encodes the caspid structural protein VP1 , VP2 and VP3 and the regulatory protein, agnoprotein. T antigen can bind to and inactivate such tumor suppressors as p53 and pRb, disrupt the Wnt and IGF signaling pathways and instablize the genome by inserting to result in tumorigenesis. Intravenous or intracranial inoculation of JCV into experimental animals or its transgenic models have been found to cause a variety of neurological tumors. In recent years, presence of JCV T antigen DNA has been suggested to correlate with malignancies of digestive and respiratory tracts and B cell lymphoma. CONCLUSIONS: JCV is closely linked to the carcinogenesis. It would be hot to establish transgenic animal of epithelial malignancies using JCV 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.
基金项目
人事部留学人员科技活动项目择优资助课题(2008-01)
教育部留学归国人员启动项目(2009-03)
辽宁省百千万人才计划(2008921066)
沈阳市科技攻关项目(1091175-1-00)
NETL
NSTL
维普
万方数据