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PB2 and hemagglutinin mutations confer a virulent phenotype on an H1N2 avian influenza virus in mice

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Abstract

We previously obtained mouse-adapted variants of H1N2 avian influenza virus that contained PB2-L134H, PB2-I647L, PB2-D701N, HA-G228S, and M1-D231N mutations. Here, we analyzed the effects of these mutations on viral pathogenicity in a mammalian model. By evaluating the virulence of mouse-adapted H1N2 variants at different generations, we found that the PB2-D701N and HA-G228S mutations both contribute to the virulence of this virus in mammals. Furthermore, we found that the PB2-D701N and HA-G228S mutations both enhance the ability of the virus to replicate in vivo and in vitro and that the PB2-D701N substitution results in an expansion of viral tissue tropism. These results suggest that the PB2-D701N mutation and the HA-G228S mutation are the major mammalian determinants of H1N2 virus. These results help us to understand more about the mechanisms by which influenza viruses adapt to mammals, and monitoring of these mutations can be used in continuous influenza surveillance to assess the pandemic potential of avian influenza virus variants.

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Acknowledgements

We thank the anonymous reviewers and the handling editor for their constructive comments on the paper. This work was supported by the Youth Foundation of the Natural Science Foundation of Shandong Province (ZR2018QC005), the National Key Technology R&D Program (2013BAD12B04), National Key Research and Development Plan (2016YFD0500203) and (2017YFD0500100), the High-Level Talents and Innovative Team Recruitment Program of the Shandong Academy of Agricultural Sciences, High-Level Talent Projects (ts201511069; W03020496), and the Construction of Subjects and Teams of the Institute of Poultry Science (CXGC2018E11).

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Authors and Affiliations

  1. Institute of Poultry Science, Shandong Academy of Agricultural Sciences, No. 1 Jiaoxiao road, Jinan, 250023, Shandong, China

    Zhijun Yu & Jiaqiang Wu

  2. Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Science of PLA, 666 Liuyingxi St., Changchun, 130122, People’s Republic of China

    Yongkun Zhao, Weiyang Sun, Xinghai Zhang, Xianzhu Xia & Yuwei Gao

  3. College of Life Sciences, Shandong Normal University, Jinan, 250014, China

    Hongbin He

  4. Dairy Cattle Research Center, Shandong Academy of Agricultural Sciences, Jinan, 250132, China

    Kaihui Cheng

  5. Joint National Laboratory for Antibody Drug Engineering, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China

    Zhiguang Ren

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  1. Zhijun Yu
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  2. Zhiguang Ren
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Correspondence to Zhijun Yu, Xianzhu Xia or Yuwei Gao.

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Yu, Z., Ren, Z., Zhao, Y. et al. PB2 and hemagglutinin mutations confer a virulent phenotype on an H1N2 avian influenza virus in mice. Arch Virol 164, 2023–2029 (2019). https://doi.org/10.1007/s00705-019-04283-0

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  • DOI: https://doi.org/10.1007/s00705-019-04283-0

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