【摘要】 【目的】研究来自不同临床类型H7N9感染者病毒分离株的致病性,探索病毒分子特性与致病差异的关系。【方法】建立人PBMC体外培养及病毒感染模型,人肺组织体外培养及病毒感染模型以及小鼠感染H7N9动物模型,分别从以上3个层次研究两株来自轻症和重症H7N9感染者病毒分离株(即GD-6和GD-7)的感染性及病理损伤状况。【结果】两株病毒均能感染人PBMC、人肺组织体外培养模型和Balb/C小鼠的肺组织,并在其中有效复制,且GD-7的增殖能力强于GD-6。病毒主要感染人肺组织的II型肺泡上皮细胞,GD-7引起肺组织的病例变化更加明显。在小鼠肺组织,GD-7的病毒载量高于GD-6,小鼠感染病毒后其肺指数增大,肺组织的病理变化明显,且GD-7对小鼠的致病力强于GD-6。【结论】重症分离株GD-7的复制能力和致病力强于轻症分离株GD-6,结合前期研究结果 ,两株病毒存在关键氨基酸位点的差异,其中PB2蛋白的627位点在GD-7发生了突变E627K,因此推测病毒载量及关键位点突变可能对病毒的致病力起重要作用。更多还原

【Abstract】 【Objective】To compare the pathogenicity of two H7N9 virus isolates from patients with different clinical outcomes and explore the relationship between molecular properties of viruses and pathogenic differences. 【Methods】Establish the H7N9 infection models of in vitro human peripheral blood mononuclear cells(PMBCs), ex vivo human lung tissues, and in vivo Balb / C mice. Analyses the infectivity and pathological damage status of two H7N9 isolates from mild and severe patients(named GD-6 and GD-7) using in vitro, ex vivo, and in vivo studies. 【Results】Both GD-6 and GD-7 could infect and replicate in vitro, ex vivo, and in vivo models and GD-7 replicated to higher levels than GD-6. They were detected predominantly in type II pneumocytes in human lung tissue culture,furthermore, GD-7 infection resulted in more severe lung damage than GD-6 infection. The two virus isolates could efficiently replicated in the lung of the mice, and the viral loads of GD-7 were higher than that of GD-6. The lung index of the mice became larger, and the lungs had histopathological change, moreover, GD-7 was more pathogenic than GD-6. 【Conclusion】The results suggest that the high viral loads and mutation E627 K in PB2 may play an important role in the pathogenesis of avian influenza A(H7N9) virus.更多还原