【Objective】 To compare the pathogenicity of two H7N8 virus isolates from patients with different clinical outcomes and explore the relationship between molecular properties of viruses and pathogenic differences. 【Methods】To 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-7could 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 E627Kin PB2 may play an important role in the pathogenesis of avian influenza A (H7N9) virus.