季节性流感病毒H1N1BALB/c鼠肺适应株的建立及其分子机制  

Establishment of a mouse-adapted seasonal H1N1 virus strain via BALB/c mice and its molecular mechanism

作　　者：李枫棣[1] 许黎黎[1] 鲍琳琳[1] 吕琦[1] 秦川[1] 

机构地区：[1]中国医学科学院医学实验动物研究所卫生部人类疾病比较医学重点实验室国家中医药管理局人类疾病动物模型三级实验室,北京100021

出　　处：《中国实验动物学报》2014年第1期22-26,共5页Acta Laboratorium Animalis Scientia Sinica

基　　金：科技重大专项--艾滋病和病毒性肝炎等重大传染病防治:2009ZX10004-016;2009ZX10004-402;2009ZX10004-503;卫生公益性行业科研专项项目:200802036;中央级公益性科研院所基本科研业务费(DWS201112)

摘　　要：目的建立季节性流感病毒H1N1的鼠肺适应株,并对适应的分子机理进行研究。方法以病毒滴鼻感染小鼠,通过在BALB/c小鼠肺组织中连续传代,观察小鼠存活情况及肺病理改变,来获得季节性流感病毒H1N1的鼠肺适应株。结果季节性流感H1N1 A/Brisbane/59/2007病毒野生型毒株,经过在小鼠体内进行8次传代后,毒力逐渐增强,从无致病力到致死率达到100%,对鼠肺适应株与野生型毒株进行基因比对,发现适应株HA基因发生了3个有义突变。结论野生季节性低致病力H1N1流感病毒可经在小鼠中经过多次传代而获得高致病力H1N1鼠肺适应株,HA蛋白89位Thr至Ile的突变对毒力的增强起决定性作用。Objective To establish adapted strain of seasonal H1N1 influenza virus in mice and infection model. Methods The mice model was induced by nose dropping method with influenza virus, by continuous passage in the lung tissue of BALB/c, to get the adapted strain of seasonal H1N1 in mice and seasonal influenza virus infection model, and the lung index and death rate was observed. Results After 8 times consecutive passages in the lung tissue of BALB/c, virulence of wild type seasonal H1N1 virus was increased to a high level. Genome sequencing and alignment indicated that the HA gene was mutated. Conclusion The virulent mouse-adapted variant A/Brisbane/59/2007-MA can be acquired from the avirulent A/Brisbane/59/2007 strain by continuous passage in the lung tissues of mice. Mutation of Thr to Ile at residue 89 of HA protein is the key virulence determinant.

关 键 词：季节性流感病毒H1N1 鼠肺适应株 感染模型 连续传代 

分 类 号：Q95-33[生物学—动物学]