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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 a lethal mouse model of influenza A (H1N1) virus infection and to provide animal models for studying pathogenicity, host adaptability and vaccine protection, and to find out the key sites that affect the virulence and adaptability of the virus in host adaptation. The new H1N1 influenza A / Sichuan / SWL1 / 2009 H1N1 mice were passaged 15 times in succession, each generation of sub-strains were proliferated on MDCK cells and sequenced. According to the sequence analysis, 6 passaged strains were selected for infection Mice, continuous monitoring of 14 d weight and death; and the 14th and 15th generation of virus cloning and sequencing analysis after plaque experiments were purified. The primary virus does not lethal to BABL / C mice, and the virulence of the host mice is enhanced by the continuous passage of the animals in the body to adapt to the host animals. Specifically, the 7th, 11th and 15th generations of the 6 selected passaged virus strains can be 100% Lethal test mice; analysis of the entire genome of the 6 passaged strains indicated that some of these strains were mutated in their amino acid positions. The new influenza A (H1N1) virus was successfully passaged in mice and a mouse lethal model was established. The enhancement of virus virulence may be related to the changes of some amino acid sites.