人类疱疹病毒6型DR7基因编码蛋白在调控人神经胶质瘤发生中的作用

Glioma is a most common malignant primary brain tumor in human beings, however its pathogen is unclear.Our preliminary studies and literature revealed that human herpesvirus 6 (HHV-6) is involved in the pathogenesis of malignant gliomas, however the exact mechanisms by which HHV-6 participates in the glioma formation are barely known. The DR7 gene of HHV-6 has thought to be a kind of transcription activator which posess important roles in the tumorigenesis of human malignant glioma through the regulation of host cell gene expression. Roles of HHV-6 DR7 protein and the underlying mechanisms will be investigated in this project. The study consists of three parts: (1) The correlation of the expression of DR7 protein and glioma will be determined by clinical investigation. (2) The effects of HHV-6 DR7 protein for the biological function of glioma cells in vivo and in vitro will be observed by using gene transfection and RNA interference technology.（3）The key molecules and signaling pathways mediated the role of HHV-6 protein in glioma will be screened and identified.The result of this project can not only lead to a better understanding of the role and mechanism of HHV-6 DR7 protein in glioma, but also it would provide theoretical and experimental foundation for the development of therapeutical and preventive vaccines for glioma.

神经胶质瘤（Glioma）是最常见的人类原发性恶性脑肿瘤，病因尚不清楚。本课题组前期研究及文献报道表明人类疱疹病毒6型（Human Herpesvirus 6，HHV-6）感染与神经胶质瘤的发生具有密切联系,但其参与机制尚不清楚。HHV-6 DR7蛋白是一种病毒编码转录激活子，被认为可能通过调控宿主细胞基因表达而影响神经胶质瘤的发生，但其相关性及参与机制仍缺乏研究。本研究拟（1）通过临床标本检测揭示HHV-6 DR7基因表达水平与胶质瘤进展及预后的相关性。（2）运用基因转染、RNA干扰等技术在体外及体内研究HHV-6 DR7蛋白对神经胶质瘤细胞生物学功能的影响。（3）筛选、验证介导HHV-6 DR7蛋白作用于神经胶质瘤细胞的关键分子及信号通路。本项目的研究结果不仅可以明确HHV-6 DR7蛋白在神经胶质瘤中所起的作用及机制，还为研究治疗及预防性抗胶质瘤疫苗提供依据。

神经胶质瘤（Glioma）是最常见的人类原发性恶性脑肿瘤，病因尚不清楚。本课题组前期研究及文献报道表明人类疱疹病毒6型（Human Herpesvirus 6，HHV-6）感染与神经胶质瘤的发生具有密切联系,但其参与机制尚不清楚。HHV-6 DR7蛋白是一种病毒编码转录激活子，被认为可能通过调控宿主细胞基因表达而影响神经胶质瘤的发生，但其相关性及参与机制仍缺乏研究。本研究结果（1）HHV-6 DR7基因表达蛋白与神经胶质瘤恶性程度成正相关，而与患者生存期成负相关；（2）HHV-6 DR7基因表达蛋白可促进神经胶质瘤细胞增殖、侵袭、迁移及血管生成等恶性表型；（3）利用表达谱芯片、ELISA及Western blot等方法证实MMP-3、TIMP-2、TIMP-4、IL-6，TP53、IL-1，ITGβ5、FN1及IL-8等分子参与了HHV-6 DR7基因作用于神经胶质瘤细胞的过程。这些研究结果部分揭示HHV-6在神经胶质瘤发生发展中的作用及可能机制，有利于新疗法的开发。