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

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 pathogenici...

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Autores principales: Zhu, Cuisong, Zhang, Miaomiao, Fu, Weihui, He, Yongquan, Yang, Yu, Zhang, Linxia, Yuan, Songhua, Jiang, Lang, Xu, Jianqing, Zhang, Xiaoyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9414078/
https://www.ncbi.nlm.nih.gov/pubmed/36034707
http://dx.doi.org/10.3389/fcimb.2022.941078
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author Zhu, Cuisong
Zhang, Miaomiao
Fu, Weihui
He, Yongquan
Yang, Yu
Zhang, Linxia
Yuan, Songhua
Jiang, Lang
Xu, Jianqing
Zhang, Xiaoyan
author_facet Zhu, Cuisong
Zhang, Miaomiao
Fu, Weihui
He, Yongquan
Yang, Yu
Zhang, Linxia
Yuan, Songhua
Jiang, Lang
Xu, Jianqing
Zhang, Xiaoyan
author_sort Zhu, Cuisong
collection PubMed
description 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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spelling pubmed-94140782022-08-27 Comparison of H7N9 and H9N2 influenza infections in mouse model unravels the importance of early innate immune response in host protection Zhu, Cuisong Zhang, Miaomiao Fu, Weihui He, Yongquan Yang, Yu Zhang, Linxia Yuan, Songhua Jiang, Lang Xu, Jianqing Zhang, Xiaoyan Front Cell Infect Microbiol Cellular and Infection Microbiology 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. Frontiers Media S.A. 2022-08-12 /pmc/articles/PMC9414078/ /pubmed/36034707 http://dx.doi.org/10.3389/fcimb.2022.941078 Text en Copyright © 2022 Zhu, Zhang, Fu, He, Yang, Zhang, Yuan, Jiang, Xu and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Zhu, Cuisong
Zhang, Miaomiao
Fu, Weihui
He, Yongquan
Yang, Yu
Zhang, Linxia
Yuan, Songhua
Jiang, Lang
Xu, Jianqing
Zhang, Xiaoyan
Comparison of H7N9 and H9N2 influenza infections in mouse model unravels the importance of early innate immune response in host protection
title Comparison of H7N9 and H9N2 influenza infections in mouse model unravels the importance of early innate immune response in host protection
title_full Comparison of H7N9 and H9N2 influenza infections in mouse model unravels the importance of early innate immune response in host protection
title_fullStr Comparison of H7N9 and H9N2 influenza infections in mouse model unravels the importance of early innate immune response in host protection
title_full_unstemmed Comparison of H7N9 and H9N2 influenza infections in mouse model unravels the importance of early innate immune response in host protection
title_short Comparison of H7N9 and H9N2 influenza infections in mouse model unravels the importance of early innate immune response in host protection
title_sort comparison of h7n9 and h9n2 influenza infections in mouse model unravels the importance of early innate immune response in host protection
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9414078/
https://www.ncbi.nlm.nih.gov/pubmed/36034707
http://dx.doi.org/10.3389/fcimb.2022.941078
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