PGRN缺失对猪血凝性脑脊髓炎病毒脑内感染小鼠的影响  

Effect of PGRN deficiency on intracerebral infection of mice with porcine hemagglutinating encephalomyelitis virus

作　　者：柳雨竹 王炳量 陈雨竹 甄理 王真真 王改丽 李姿 石俊超 兰云刚 宋德光 LIU Yuzhu;WANG Bingliang;CHEN Yuzhu;ZHEN Li;WANG Zhenzhen;WANG Gaili;LI Zi;SHI Junchao;LAN Yungang;SONG Deguang(College of Veterinary Medicine,Jilin University,Changchun 130062,China;Hebei Rural Revitalization Promotion Center,Shijiazhuang 050000,China;Jilin Province Animal Husbandry and Veterinary Academy of Sciences,Changchun 130062,China)

机构地区：[1]吉林大学动物医学学院,吉林长春130062 [2]河北省乡村振兴促进中心,河北石家庄050000 [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》2023年第10期2072-2077,共6页Chinese Journal of Veterinary Science

基　　金：国家自然科学基金资助项目(32172804);中国博士后科学基金资助项目(2020M670858)。

摘　　要：已有研究表明溶酶体与β冠状病毒复制密切相关,为研究调控溶酶体功能的关键蛋白颗粒蛋白前体(progranulin,PGRN)对β冠状病毒猪血凝性脑脊髓炎病毒(porcine hemagglutinating encephalomyelitis virus,PHEV)复制的影响,本研究以PGRN缺失及其对照小鼠为研究对象,探究PGRN在PHEV脑内感染小鼠过程中的作用。研究发现,与PHEV脑内感染野生型小鼠相比,PGRN缺失小鼠脑内感染病毒后其存活时间延长,同时脑内病毒含量显著降低,细胞因子IFN和TNF-a的含量升高;此外,神经退行性病变相关蛋白TDP-43表达显著升高,表明PGRN缺失能减缓病毒的复制,增强免疫反应,并影响病毒的致病性。研究结果为进一步揭示溶酶体蛋白PGRN在PHEV复制过程中的作用机制提供研究基础,并为β冠状病毒致病机制研究提供参考。It has been shown that lysosomes are closely associated with β-coronavirus replication.To investigate the effect of the key protein particle protein progranulin(PGRN),which regulates lysosome function,on β-coronavirus porcine hemagglutinating encephalomyelitis virus(PHEV)replication,the role of PGRN in the process of PHEV intracerebral infection in mice with PGRN deficiency and its control mice was investigated.It was found that PGRN-deficient mice survived longer after intracerebral infection with the virus compared to PHEV-infected wild-type mice,while intracerebral viral levels were significantly lower and cytokine IFN and TNF-a levels were higher;in addition,the expression of the neurodegenerative disease-associated protein TDP-43 was significantly higher,indicating that PGRN deficiency slowed viral replication,enhanced the immune response,and affected viral pathogenicity.The results of the study provide a research basis to further reveal the role of the lysosomal protein PGRN in the replication process of PHEV and provide a reference for the study of the pathogenesis of β-coronavirus.

关 键 词：猪血凝性脑脊髓炎病毒 颗粒蛋白前体 病毒复制 

分 类 号：S852.65[农业科学—基础兽医学]