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PNAS: A Eurasian avian-like H1N1 swine influenza reassortant virus became pathogenic and highly transmissible due to mutations in its PA gene

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  • PNAS: A Eurasian avian-like H1N1 swine influenza reassortant virus became pathogenic and highly transmissible due to mutations in its PA gene

    Source: https://www.pnas.org/doi/10.1073/pnas.2203919119

    A Eurasian avian-like H1N1 swine influenza reassortant virus became pathogenic and highly transmissible due to mutations in its PA gene
    Fei Meng, Huanliang Yang, Zhiyuan Qu, +7 , Yan Chen, Yijie Zhang, Yaping Zhang, Liling Liu, Xianying Zeng, Chengjun Li, Yoshihiro Kawaoka https://orcid.org/0000-0001-5061-8296 yoshihiro.kawaoka@wisc.edu, and Hualan Chen chenhualan@caas.cn -7Authors Info & Affiliations
    Contributed by Yoshihiro Kawaoka; received March 16, 2022; accepted June 18, 2022; reviewed by Amy Vincent Baker, Juergen Richt, and Terrence Tumpey
    August 15, 2022
    119 (34) e2203919119
    https://doi.org/10.1073/pnas.2203919119

    Significance
    Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses have been circulating in pigs in many European and Asian countries and have caused multiple human infections throughout Europe and China. In this study, we found that an EA H1N1 reassortant isolated from pigs in China has become pathogenic in mice and transmissible in ferrets, posing an increased threat to public health. We further found that this EA H1N1 virus obtained these harmful characteristics by accumulating mutations in its acidic polymerase (PA) gene and that the PA gene bearing these mutations was predominant in the 2009/H1N1 viruses in humans and progressively increased in the 2009/H1N1 viruses in swine. Our study emphasizes the importance of monitoring and evaluating the EA H1N1 viruses in pigs for their pandemic potential.

    Abstract
    Previous studies have shown that the Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses circulated widely in pigs around the world and formed multiple genotypes by acquiring non-hemagglutinin and neuraminidase segments derived from other swine influenza viruses. Swine influenza control is not a priority for the pig industry in many countries, and it is worrisome that some strains may become more pathogenic and/or transmissible during their circulation in nature. Our routine surveillance indicated that the EA H1N1 viruses obtained different internal genes from different swine influenza viruses and formed various new genotypes. In this study, we found that a naturally isolated swine influenza reassortant, A/swine/Liaoning/265/2017 (LN265), a representative strain of one of the predominant genotypes in recent years, is lethal in mice and transmissible in ferrets. LN265 contains the hemagglutinin, neuraminidase, and matrix of the EA H1N1 virus; the basic polymerase 2, basic polymerase 1, acidic polymerase (PA), and nucleoprotein of the 2009 H1N1 pandemic virus; and the nonstructural protein of the North American triple-reassortment H1N2 virus. By generating and testing a series of reassortants and mutants, we found that four gradually accumulated mutations in PA are responsible for the increased pathogenicity and transmissibility of LN265. We further revealed that these mutations increase the messenger RNA transcription of viral proteins by enhancing the endonuclease cleavage activity and viral RNA–binding ability of the PA protein. Our study demonstrates that EA H1N1 swine influenza virus became pathogenic and transmissible in ferrets by acquiring key mutations in PA and provides important insights for monitoring field strains with pandemic potential.
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