Zhu C, Zhang M, Fu W, He Y, Yang Y, Zhang L, Yuan. Comparison of H7N9 and H9N2 influenza infections in mouse model unravels the importance of early innate immune response in host protection. Front Cell Infect Microbiol. 2022 Aug 12;12:941078
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 humans, causing high mortality and emerged as a potential pandemic threat. The mechanisms underlying the virulence and pathogenicity of H7N9 virus remains elusive. H7N9 virus originated from a genetic assortment that involved the 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 the mouse infection model to dissect the difference in the host response between the H7N9 and H9N2 viruses. Through analyzing transcriptomics of infected lungs, we surprisingly found that the H9N2 infection elicited an earlier induction of innate immunity than H7N9 infection. This finding was further corroborated by an immunohistochemical study demonstrating earlier recruitment of macrophage to the H9N2-infected lung than the 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 the H9N2 virus protected mice from the challenge of both H7N9 and PR8 viruses, thereby strengthening the importance of the induction of an early innate immunity in the host´s defense against influenza infection. Collectively, our study unraveled a previously unidentified difference in host response between H7N9 and H9N2 infection and shed new insight on how virus-host interaction shapes the in vivo outcome of influenza infection.
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