AUTHOR=Zhu Cuisong , Zhang Miaomiao , Fu Weihui , He Yongquan , Yang Yu , Zhang Linxia , Yuan Songhua , Jiang Lang , Xu Jianqing , Zhang Xiaoyan 

TITLE=Comparison of H7N9 and H9N2 influenza infections in mouse model unravels the importance of early innate immune response in host protection

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.941078

DOI=10.3389/fcimb.2022.941078

ISSN=2235-2988

ABSTRACT=The outcome of infection with influenza A virus is determined by a complex virus-host interaction. A new H7N9 virus of avian origin crossed the species barrier to infect human, causing high morality, and emerged as a potential pandemic threat. The mechanisms underlying the virulence and pathogenicity of H7N9 virus remains elusive.  H7N9 virus originated from genetic assortment that involved avian H9N2 virus, which was the donor of the six internal genes.  Unlike the H7N9 virus, the H9N2 virus caused only mild phenotype in infected mice.  In this study, we used mouse infection model to dissect the difference in host response between H7N9 and H9N2 virus.   Through analyzing transcriptomics of infected lungs, we surprisingly found H9N2 infection elicited an earlier induction of innate immunity than H7N9 infection. This finding was further corroborated by immunohistochemical study demonstrating earlier recruitment of macrophage to H9N2-infected lung than H7N9-infected lung, which could occur as early as 6 hours post infection.  In contrast, H7N9 infection was characterized by a late, strong lung CD8+ T cell response that is more robust than H9N2 infection.  The different pattern of immune response may underlie more severe lung pathology caused by H7N9 infection compared to H9N2 infection.  Finally, we could show that co-infection of H9N2 virus protected mice from challenge of both H7N9 and PR8 viruses, thereby strengthening the importance of the induction of an early innate immunity in host defense against influenza infection.  Collectively, our study unraveled a previously unidentified difference in host response between H7N9 and H9N2 infection and shed new insight into how virus-host interaction shapes the in vivo outcome of influenza infection.