PI3K-Akt-Rho A通路在猪血凝性脑脊髓炎病毒入侵N2a细胞中的调控作用  

Regulation of PI3K-Akt-Rho A pathway in porcine hemagglutinating encephalomyelitis virus invasion of N2a cells

作　　者：周倩宇 吕晓玲 王改丽 李姿 贺文琦 ZHOU Qianyu;LYU Xiaoling;WANG Gaili;LI Zi;HE Wenqi(College of Veterinary Medicine,Jilin University,Changchun 130062,China;College of Veterinary Medicine,Shanxi Agricultural University,Jinzhong,Shanxi 030800,China;Animal Husbandry and Veterinary Research Institute of Jilin Province,Changchun 130062,China)

机构地区：[1]吉林大学动物医学学院,吉林长春130062 [2]山西农业大学动物医学学院,山西晋中030800 [3]吉林省畜牧兽医科学研究院,吉林长春130062

出　　处：《中国兽医学报》2022年第5期841-845,共5页Chinese Journal of Veterinary Science

基　　金：国家自然科学基金资助项目(31872446,31902262);吉林省科技发展计划资助项目(20210202041NC)。

摘　　要：猪血凝性脑脊髓炎病毒(PHEV)为嗜神经性冠状病毒,主要侵害宿主中枢神经系统诱发神经变性损伤性疾病。神经细胞结构与功能的维持与细胞骨架重塑密切相关。本研究对细胞骨架相关分子进行检测,通过Western blot检测PHEV入侵N2a神经细胞后PI3K及其下游分子Akt的蛋白表达量,发现PHEV感染早期p-PI3K和p-Akt的蛋白表达量均增高,表明PI3K-Akt信号通路被激活。随后通过Western blot、RT-qPCR和IFA证明PI3K-Akt信号通路及该信号通路下游底物小G蛋白Rho A参与调控肌动蛋白(F-actin)骨架的动态重塑,并促进病毒入侵N2a神经细胞。综上所述,PHEV入侵可劫持宿主PI3K-Akt-Rho A信号通路并诱导F-actin细胞骨架重塑,这一分子机制的揭示可为抗病毒药物筛选提供新的靶标。Porcine haemagglutinating encephalomyelitis virus(PHEV),a neurotropic coronavirus,invades host central nervous system and causes neurodegenerative disease.The maintenance of nerve structure and function is closely related to cytoskeleton remodeling.In this study,cytoskeleton-related molecules were detected,Western blot was used to detect the protein expression levels of PI3 K and its downstream molecule Akt after PHEV invaded N2 a nerve cells.It was found that the protein expression levels of P-PI3 K and P-Akt were both increased in the early stage of PHEV infection,indicating that the PI3 K-Akt signaling pathway was activated.Subsequently,Western blot,RT-qPCR and IFA showed that the PI3 K-Akt signaling pathway and its downstream substrate,small G protein Rho A,were involved in regulating the dynamic remodeling of the F-actin skeleton and promoting the invasion of N2 a nerve cells by virus.Thus,we concluded that PHEV invasion hijacks host PI3 K-Akt-Rho A signal and induces F-actin cytoskeleton remodeling,the discovery of this molecular mechanism may provide a new target for antiviral drug screening.

关 键 词：猪血凝性脑脊髓炎病毒 F-ACTIN PI3K Akt Rho A 病毒入侵 

分 类 号：S852.65[农业科学—基础兽医学]