Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses.

Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses.
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DOI:
10.1038/ncomms3636
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发表时间:
2013
影响因子:
16.6
通讯作者:
Friedrich, Thomas C.
Friedrich, Thomas C.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wilker, Peter R.;Dinis, Jorge M.;Starrett, Gabriel;Imai, Masaki;Hatta, Masato;Nelson, Chase W.;O'Connor, David H.;Hughes, Austin L.;Neumann, Gabriele;Kawaoka, Yoshihiro;Friedrich, Thomas C.

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人传播H5 N1禽流感病毒的出现构成了大流行病的重大威胁。H5 N1病毒被认为在宿主之间和宿主内具有高度的遗传多样性,但对这种多样性对病毒复制和传播的影响知之甚少。在这里,我们使用深度测序来研究宿主内病毒变异对H5 N1病毒在雪貂中的适应和传播的影响。我们发现,虽然在接种雪貂复制过程中,血凝素(HA)的宿主内遗传多样性增加,但HA多样性在呼吸道飞沫传播后显著降低,其中感染仅由来自传播动物中不同来源病毒群体的1-2个不同HA片段建立。此外,源动物中仅5.9%的病毒中存在的微小HA变体在通过呼吸道飞沫感染的雪貂中占主导地位。这些发现表明,在哺乳动物之间的流感病毒传播过程中的选择压力施加了一个重大的瓶颈。
The emergence of human-transmissible H5N1 avian influenza viruses poses a major pandemic threat. H5N1 viruses are thought to be highly genetically diverse both among and within hosts, but the effects of this diversity on viral replication and transmission are poorly understood. Here we use deep sequencing to investigate the impact of within-host viral variation on adaptation and transmission of H5N1 viruses in ferrets. We show that although within-host genetic diversity in hemagglutinin (HA) increases during replication in inoculated ferrets, HA diversity is dramatically reduced upon respiratory droplet transmission, where infection is established by only 1–2 distinct HA segments from a diverse source virus population in transmitting animals. Moreover, minor HA variants present in as little as 5.9% of viruses within the source animal become dominant in ferrets infected via respiratory droplets. These findings demonstrate that selective pressures acting during influenza virus transmission among mammals impose a significant bottleneck.
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