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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses
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High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses

机译:禽H9N2和大流行H1N1 / 2009流感病毒衍生的重组子具有高遗传相容性并增加了致病性

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摘要

H9N2 influenza viruses have been circulating worldwide in multiple avian species and repeatedly infecting mammals, including pigs and humans, posing a significant threat to public health. The coexistence of H9N2 and pandemic influenza H1N1/2009 viruses in pigs and humans provides an opportunity for these viruses to reassort. To evaluate the potential public risk of the reassortant viruses derived from these viruses, we used reverse genetics to generate 127 H9 reassortants derived from an avian H9N2 and a pandemic H1N1 virus, and evaluated their compatibility, replication ability, and virulence in mice. These hybrid viruses showed high genetic compatibility and more than half replicated to a high titer in vitro. In vivo studies of 73 of 127 reassortants revealed that all viruses were able to infect mice without prior adaptation and 8 reassortants exhibited higher pathogenicity than both parental viruses. All reassortants with higher virulence than parental viruses contained the PA gene from the 2009 pandemic virus, revealing the important role of the PA gene from the H1N1/2009 virus in generating a reassortant virus with high public health risk. Analyses of the polymerase activity of the 16 ribonucleoprotein combinations in vitro suggested that the PA of H1N1/2009 origin also enhanced polymerase activity. Our results indicate that some avian H9-pandemic reassortants could emerge with a potentially higher threat for humans and also highlight the importance of monitoring the H9-pandemic reassortant viruses that may arise, especially those that possess the PA gene of H1N1/2009 origin.
机译:H9N2流感病毒已在​​全球范围内在多种鸟类中传播,并反复感染包括猪和人在内的哺乳动物,对公共健康构成了重大威胁。 H9N2和大流行性流感H1N1 / 2009病毒在猪和人中的共存为这些病毒提供了重新组合的机会。为了评估衍生自这些病毒的重组病毒的潜在公共风险,我们使用反向遗传学产生了来自禽类H9N2和大流行性H1N1病毒的127种H9重分类子,并评估了它们的相容性,复制能力和小鼠毒性。这些杂种病毒显示出高遗传相容性,并且有一半以上在体外复制到高滴度。对127个重组子中的73个进行的体内研究表明,所有病毒都能够在没有事先适应的情况下感染小鼠,并且8个重组子均比两种亲本病毒都具有更高的致病性。具有比亲本病毒更高的毒力的所有重配体均含有2009年大流行病毒的PA基因,这揭示了H1N1 / 2009病毒的PA基因在产生具有高公共卫生风险的重配体病毒中的重要作用。体外对16种核糖核蛋白组合的聚合酶活性的分析表明,H1N1 / 2009来源的PA也增强了聚合酶活性。我们的结果表明,一些禽类H9大流行性重组病毒可能对人类造成更高的威胁,并且还强调了监视可能出现的H9大流行性重组病毒的重要性,尤其是那些具有H1N1 / 2009起源的PA基因的病毒。

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    Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;

    Chinese National Influenza Center, State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China;

    Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;

    Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;

    Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;

    Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;

    Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China;

    Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;

    Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China;

    Chinese National Influenza Center, State Key Laboratory for Molecular Virology and Genetic Engineering, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China;

    Key Laboratory of Zoonosis of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China The Shandong Animal Disease Control Center, Jinan, Shandong 250022, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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