摘要
建立新甲型H1N1流感病毒小鼠致死模型,为研究致病性、宿主适应性以及疫苗保护性提供动物模型,并寻找病毒在适应宿主过程中影响毒力和适应性的关键位点。将新甲型H1N1流感病毒A/四川/SWL1/2009 H1N1在小鼠中连续传15代,各代次毒株均在MDCK细胞上增殖后进行测序,根据序列分析结果选择6个传代毒株感染小鼠,连续监测14 d体重和死亡情况;并对第14代和15代病毒在噬斑实验纯化后克隆和测序分析。原代病毒不致死BABL/C小鼠,经动物体内连续传代适应宿主动物后,其毒力增强,具体表现为所选的6个传代毒株中第7、11、15代毒株可以100%致死试验小鼠;分析这6个传代毒株的全基因组表明这些毒株的部分氨基酸位点发生突变。新甲型H1N1流感病毒经小鼠体内连续传代后,建立了小鼠致死模型,病毒毒力增强可能与某些氨基酸位点的改变有关。
To establish the mouse-lethal model for pandemic H1N1 influenza virus,provide an animal model for studying the pathogenicity and host adaptation of 2009 pandemic H1N1 influenza virus,and find out the key amino acid mutations which may affect viral virulence and replication.A pandemic H1N1 influenza virus strain,A/Sichuan/SWL1/2009（H1N1,SC/1） was passaged in mouse lung by 15 cycles with intranasal infection.The passaged viruses were all propagated in MDCK cells and sequenced.Based on the sequencing results,four mice in each group were inoculated with 6 selected viruses and their weight and survival rate were monitored during the following 14 days after infection.Additionally,SC/1-MA P14 and P15 viruses were sequenced after purification by Plague Assay.Viral virulence was increased after serial passages and the mortality of 100% was detected after 7 passages.Several amino acid residue mutations of passaged viruses which may contribute to the enhanced virulence were observed.The increased virulence of passaged viruses and mammalian host adaptation maybe associated with amino acid mutations in viral functional proteins.Finally,we established a mouse-lethal model.
出处
《病毒学报》
CAS
CSCD
北大核心
2011年第2期103-107,共5页
Chinese Journal of Virology
基金
国家973课题2011CB504704
