新型三源重组H1N1亚型猪流感病毒的遗传进化与分子致病机制研究

猪流感（SI）是危害养猪业的一种重要疾病，其病原猪流感病毒（SIV）对人类健康也有潜在威胁。现有报道表明：欧洲类禽H1N1亚型SIV是国内重要的流行株，并与其它SIV重组为新型三源重组H1N1亚型SIV，这种新型重组SIV已具备感染人的能力。我们前期数据表明：这种新型三源重组SIV在国内部分猪群中流行；与欧洲类禽SIV相比，新型三源重组SIV在哺乳动物模型（猪和小鼠）体内的致病力明显增强，但其分子机制还不清楚。本研究将继续加强新型三源重组SIV监测及遗传进化研究，构建欧洲类禽和新型三源重组SIV的反向遗传操作技术平台，进行RNP（PB2、PB1、PA及NP）和NS基因片段替换或点突变的病毒拯救，进而运用细胞和哺乳动物感染模型，揭示RNP和NS致病关键基因及位点在SIV复制与致病过程中所发挥的作用，解析新型三源重组SIV在哺乳动物体内致病力增强的分子机制，为新型SIV防控提重要的理论数据。

Swine influenza (SI) is an important disease that greatly endangers swine industry, and its pathogen, swine influenza virus (SIV), is also a potential threat to human health. Many studies suggest that the European avian like H1N1 subtype SIV lineage has become prevalent in China, and the novel triple-reassortant H1N1 SIV containing the genes from European avian like H1N1 subtype SIV and other influenza viruses has emerged, and this novel virus has the ability to infect humans. Our preliminary data show that this novel triple-reassortant SIV is prevalent in some provinces in China ; compared with the Eurasian avian H1N1 subtype SIV, the pathogenicity of this novel SIV in mammalian model (pigs and mice) was enhanced, but the molecular pathogenesis is not clear. In this study, we will strengthen the monitoring and genetic evolution of this novel triple-reassortant SIV. Then a series of reassortant or mutated SIVs with different RNP (PB2, PB1, PA and NP) and NS genes will be rescued using the reverse genetic systems of the triple-reassortant H1N1 SIV and European avian like H1N1 subtype SIV. Finally, the biological characteristics of these reassortant viruses, such as growth curve in vitro, plaque morphology, polymerase activity in 293T cell, replication and pathogenicity in mice and pigs, the expressions of cytokines and transcript profiling in lungs of mice and pigs, will be investigated. In conclusion, our study will reveal the pathogenesis of the triple-reassortant H1N1 SIV and provide important theoretical data for the prevention and control of SIVs.