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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence
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Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence

机译:禽H5N1和人类H3N2流感病毒之间的重配产生具有高毒力的杂交病毒

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摘要

The spread of avian H5N1 influenza viruses around the globe has become a worldwide public health concern. To evaluate the pathogenic potential of reassortant viruses between currently cocirculating avian H5N1 and human H3N2 influenza viruses, we generated all the 254 combinations of reassortant viruses between A/chicken/South Kalimantan/UT6028/06 (SK06, H5N1) and A/ Tokyo/Ut-Sk-1/07 (Tok07, H3N2) influenza viruses by reverse genetics. We found that the presence of Tok07 PB2 protein in the ribonucleoprotein (RNP) complex allowed efficient viral RNA transcription in a minigenome assay and that RNP activity played an essential role in the viability and replicative ability of the reassortant viruses. When the pathogenicity of 75 reassortant H5 viruses was tested in mice, 22 were more pathogenic than the parental SK06 virus, and three were extremely virulent. Strikingly, all 22 of these viruses obtained their PB2 segment from Tok07 virus. Further analysis showed that Tok07 PB1 alone lacked the ability to enhance the pathogenicity of the reassortant viruses but could do so by cooperating with Tok07 PB2. Our data demonstrate that reassortment between an avian H5N1 virus with low pathogenicity in mice and a human virus could result in highly pathogenic viruses and that the human virus PB2 segment functions in the background of an avian H5N1 virus, enhancing its virulence. Our findings highlight the importance of surveillance programs to monitor the emergence of human H5 reassortant viruses, especially those containing a PB2 segment of human origin.
机译:禽H5N1流感病毒在全球范围内的传播已成为全球公共卫生关注的焦点。为了评估当前正在传播的禽H5N1和人类H3N2流感病毒之间重配病毒的致病潜力,我们生成了A /鸡/南加里曼丹/ UT6028 / 06(SK06,H5N1)和A /东京/东京之间的254种重配病毒组合-Sk-1 / 07(Tok07,H3N2)流感病毒的反向遗传学分析。我们发现在核糖核蛋白(RNP)复合物中Tok07 PB2蛋白的存在允许在微型基因组测定中进行有效的病毒RNA转录,并且RNP活性在重配病毒的活力和复制能力中起着至关重要的作用。在小鼠中测试了75种重组H5病毒的致病性后,有22种病毒比亲本SK06病毒更具致病性,其中3种具有极强的毒性。令人惊讶的是,所有这22种病毒都从Tok07病毒获得了PB2片段。进一步的分析表明,单独的Tok07 PB1缺乏增强重配病毒的致病性的能力,但可以通过与Tok07 PB2合作来实现。我们的数据表明,在小鼠中低致病性的禽H5N1病毒与人类病毒之间的重排可能导致高致病性病毒,而人类病毒PB2片段在禽H5N1病毒的背景下起作用,增强了其毒性。我们的发现强调了监视程序对监视人类H5重配病毒尤其是含有人类起源PB2片段的病毒的出现的重要性。

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  • 作者单位

    Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711;

    Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711;

    Faculty of Veterinary Medicine and Tropical Disease Centre, Airlangga University, Surabaya 60115, Indonesia Collaborating Research Center-Emerging and Reemerging Infectious Diseases, Tropical Disease Centre, Airlangga University, Surabaya 60115, Indonesia;

    Division of Virology, Department of Microbiology and Immunology and Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan;

    Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711;

    Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711;

    Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711 Division of Virology, Department of Microbiology and Immunology and Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan Infection-Induced Host Responses Project, Exploratory Research for Advanced Technology, Saitama 332-0012, Japan;

  • 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);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    influenza reassortants; pathogenicity; pandemic;

    机译:流感重排致病性大流行;

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