The Molecular Pathogenesis Of Classical Swine H1N1 Subtype Influenza Virus Related To The Enhanced Virulence In Mammals

Genetic mutation or reassortment associated with cross-species adaptation usually involve in enhanced virulence,which are thought to be the driving factors for the early evolution of influenza A virus.Classical swine H1N1 subtype influenza virus has been circulating worldwide since it was first isolated,infected humans repeatedly,even resulted in grave consequence of people death.In China,classical swine H1N1 subtype influenza virus is predominant strain in pigs,which may cause the next influenza pandemic in the crowd by crossing interspecific barrier.However,the molecular pathogenesis of classical swine H1N1 subtype influenza virus related to the increased virulence in mammals remains poorly understood.In our studies,BALB/c mice was used as a mammalian model to simulate the process of classical swine H1N1 subtype influenza virus adaptated to the new host.The mouse-adapted strain of G11-MA with significantly enhanced virulence was obtained after 13 sequential lung passages in mice for the wild-type strain of G11-WT.The virulence of G11-MA with 50%mice lethal dose of 3.3log₁₀TCID₅₀was at least 10³ times higher than that of G11-WT.To evaluate the effects after the adaptation of classical swine H1N1 subtype influenza virus in mammals,RNA-sequencing technology was used to analyze the difference of mRNA in lungs of mice infected with different viruses.In our studies,a total of 47719 genes were detected,and 7118 genes were differential expression based on criterions of FDR...