森林脑炎病毒不同感染途径对小鼠模型的感染性分析  

Infectivity of tick-borne encephalitis virus by various routes in mouse model

作　　者：刘双军 李景良 王颖 苗会 拱小棠 刘晶晶[2] 孙宏亮 姜崴 李玉华[2] LIU Shuang-jun;LI Jing-liang;WANG Ying;MIAO Hui;GONG Xiao-tang;LIU Jing-jing;SUN Hong-liang;JIANG Wei;LI Yu-hua(Changchun Institute of Biological Products Co.,Ltd.,Changchun 130012,Jilin Province,China)

机构地区：[1]长春生物制品研究所有限责任公司,吉林长春130012 [2]中国食品药品检定研究院,北京102629

出　　处：《中国生物制品学杂志》2020年第3期260-265,共6页Chinese Journal of Biologicals

基　　金：中国重大新药创制科技重大专项——创新生物技术药评价及标准化关键技术研究(2018ZX09101001-002-002)。

摘　　要：目的分析森林脑炎病毒不同感染途径对小鼠模型的致病性、病毒分布及增殖动态。方法将适应原代地鼠肾(primary hamster kidney,PHK)细胞的森林脑炎病毒进行10倍系列稀释,取4个连续稀释度的病毒液,分别通过脑腔注射、灌胃、滴鼻、肌肉注射、腹腔注射的感染方式,对昆明小鼠进行攻毒,逐日连续观察14 d,计算半数致死量(median lethal dose,LD50);并分别取攻毒后第3、5、7天发病典型的腹腔感染组小鼠脑、肺、肾脏、肝脏、心脏、小肠、血液7种组织器官,采用蚀斑法检测病毒滴度。结果脑腔、灌胃、滴鼻、肌肉注射和腹腔注射攻毒方式的LD50分别为10、105.1、105、101.2和102PFU/mL。所有攻毒途径小鼠的脑腔中病毒滴度最高,达109PFU/mL,肺组织为106.5PFU/mL,肾脏为105PFU/mL,心脏和肝脏中病毒滴度较低,分别为102和101.5PFU/mL,肠道中出现一过性病毒感染,而血液中病毒滴度最高为105.5PFU/mL。结论森林脑炎病毒可通过多种途径感染小鼠模型,除具有较强易感性的脑组织外,对肺组织细胞同样具有较强的感染性。Objective To analyze the pathogenicity,distribution and proliferation dynamics of tick-borne encephalitis virus(TBEV) by various infection routes in mouse model. Methods The forest encephalitis virus adapted to primary hamster kidney cells was 10-fold serially diluted. Kunming mice were challenged with the virus at four consecutive dilutions by intracerebral injection,gavage,intranasal drip,intramuscular injection and intraperitoneal injection separately and observed for 14 d to calculate the medium lethal dose(LD50). The brain,lung,kidney,liver,heart,intestine and blood of mice with typical signs of morbidity on days 3,5 and 7 after challenge by intraperitoneal injection were collected and determined for virus titer by plaque assay. Results The LD50 of the virus by intracerebral injection,gavage,intranasal drip,intramuscular injection and intraperitoneal injection were 10,105. 1,105,101. 2 and 102 PFU/mL respectively. The virus titer in brain of mice challenged by various routes was the highest,which was 109 PFU/mL,while those in lung,kidney,heart and liver were 106. 5,105,102 and 101. 5 PFU/mL respectively. There was a transient virus infection in intestine,and the virus titer in blood was 105. 5 PFU/mL at most. Conclusion The mouse model was infected by TBEV through various routes. TBEV showed high susceptibility to lung cells besides nerves cells.

关 键 词：森林脑炎病毒 小鼠模型 感染性 原代地鼠肾细胞 蚀斑滴度 

分 类 号：R373.31[医药卫生—病原生物学]