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01-04-2020 | Influenza Virus | Original Investigation

Mouse adaptation of the H9N2 avian influenza virus causes the downregulation of genes related to innate immune responses and ubiquitin-mediated proteolysis in mice

Authors: Jing Guo, Xinxin Gao, Baotao Liu, Yubao Li, Wenqiang Liu, Jianbiao Lu, Cheng Liu, Rui Xue, Xuyong Li

Published in: Medical Microbiology and Immunology | Issue 2/2020

Abstract

H9N2 avian influenza viruses sporadically infect humans worldwide. These viruses have also contributed internal genes to H5N1, H5N6, H7N9, and H10N8 viruses, which have been isolated from humans with infections and are a substantial public health threat. To investigate the potential pathogenic mechanism of the H9N2 virus, we performed serial lung-to-lung passage of an avirulent H9N2 avian influenza virus (A/Chicken/Shandong/416/2016 [SD/416]) in mice to increase the pathogenicity of this virus. We generated a mouse-adapted (MA) virus that exhibited increased viral titers in the lungs, caused severe lung damage in mice, and induced body weight loss in mice; however, the avirulent parental virus did not cause any clinical symptoms in infected mice. Global gene expression analysis was performed and indicated that the transcriptional responses of these viruses were distinct. The lungs of mice infected with the MA virus exhibited the downregulation of genes related to innate immunity and ubiquitin-mediated proteolysis, which was not seen in infections with the avirulent parental virus. These data indicated that the MA virus might evade immune surveillance and changed its replication capacity to increase the viral replication level and pathogenicity. Our study demonstrates that host factors play an important role in the adaptive evolution of influenza virus in new hosts.

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Title: Mouse adaptation of the H9N2 avian influenza virus causes the downregulation of genes related to innate immune responses and ubiquitin-mediated proteolysis in mice
Authors: Jing Guo
Xinxin Gao
Baotao Liu
Yubao Li
Wenqiang Liu
Jianbiao Lu
Cheng Liu
Rui Xue
Xuyong Li
Publication date: 01-04-2020
Publisher: Springer Berlin Heidelberg
Keyword: Influenza Virus
Published in: Medical Microbiology and Immunology / Issue 2/2020
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI: https://doi.org/10.1007/s00430-020-00656-4

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