HCMV感染通过EGFR介导的MAPK-ATF5通路影响脑胶质瘤干细胞增殖及分化的机制

Malignant glioma, the most common subtype of primary brain tumor, is a type of aggressive, highly invasive, and neurologically destructive tumors considered among the deadliest of human cancers. Interestingly, several reports have confirmed that human cytomegalovirus (HCMV) sequences and viral gene expression exist in most malignant gliomas, while not in surrounding normal brain, and HCMV could modulate the malignant phenotype in gliomas by interacting with key signaling pathways, indicating a potential association between gliomas and HCMV. This research will focus on the molecular mechanism that HCMV infection activating brain tumor stem cells proliferation and differentiation through EGFR/MAPK/ATF5. Firstly the expression and location of CD133, IE86, EGFR and ATF5 will be detected in paraffin sections of surgically excised glioma by immunohistochemistry staining. Then brain tumor stem cells will be obtained both from long term in vitro cultured glioma cell lines and fresh glioma tissues by CD133 magnetic cell sorting and injected into brain to establish a SCID mice model bearing brain tumor stem cells.This study will find out the molecular mechanism that HCMV infection affecting brain tumor stem cells through EGFR/MAPK/ATF5. The mechanism and effect that HCMV infection activating brain tumor stem cells proliferation and differentiation will be studied in vitro and in vivo.This research is trying to clarify the molecular relationship between HCMV latent infection and brain tumor cellsproliferation and differentiation. It will provide new drug targets and preventions of diseases for HCMV latent infection.

人巨细胞病毒(HCMV)感染与恶性脑胶质瘤关系密切。本项目围绕HCMV感染CD133+脑胶质瘤干细胞，研究病毒通过表皮生长因子受体（EGFR）介导MAPK-ATF5通路活化，从而促进细胞增殖、抑制其分化的机制。首先利用免疫组织化学技术检测脑胶质瘤临床样本中干细胞标志CD133，HCMV即刻早期蛋白IE86,EGFR及ATF5的表达和定位；进而利用免疫磁珠分离培养CD133+脑胶质瘤干细胞，并经颅内定位注射SCID鼠，建立人脑胶质瘤干细胞SCID鼠大脑移植瘤模型，在分子水平探讨EGFR介导的MAPK-ATF5信号通路参与感染影响肿瘤干细胞生物学活性的分子机制，在细胞水平研究感染对胶质瘤干细胞增殖和分化的影响，在整体水平确证感染对神经胶质瘤干细胞生物学行为的影响及其机制。研究试图阐明HCMV感染参与脑胶质瘤发生发展的机制，为治疗HCMV持续性感染的相关疾病提供新药物靶位和防控新思路。

人巨细胞病毒(HCMV)感染与恶性脑胶质瘤关系密切。本项目围绕HCMV感染CD133脑胶质瘤干细胞通过表皮生长因子受体（EGFR）介导MAPK-ATF5通路活化，从而促进细胞增殖、抑制其分化的机制展开研究。首先利用免疫荧光技术检测脑胶质瘤临床样本中干细胞标志CD133，HCMV即刻早期蛋白IE86,EGFR及ATF5的表达和定位；进而利用免疫磁珠分离培养CD133+脑胶质瘤干细胞，并经颅内定位注射SCID鼠，建立人脑胶质瘤干细胞裸鼠大脑移植瘤模型，在分子水平探讨EGFR介导的MAPK-ATF5信号通路参与感染影响肿瘤干细胞生物学活性的分子机制，在细胞水平研究感染对胶质瘤干细胞增殖和分化的影响，在整体水平确证感染对脑神经胶质瘤干细胞生物学行为的影响及其机制。研究阐明了在HCMV感染参与脑胶质瘤发生发展的机制，为治疗HCMV持续性感染的相关疾病提供新药物靶位和防控新思路。