Eurasian-origin gene segments contribute to the transmissibility, aerosol release, and morphology of the 2009 pandemic H1N1 influenza virus.

Eurasian-origin gene segments contribute to the transmissibility, aerosol release, and morphology of the 2009 pandemic H1N1 influenza virus.
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DOI:
10.1371/journal.ppat.1002443
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发表时间:
2011-12
期刊:
影响因子:
6.7
通讯作者:
Subbarao K
Subbarao K
中科院分区:
医学1区
文献类型:
--
作者:
Lakdawala SS;Lamirande EW;Suguitan AL Jr;Wang W;Santos CP;Vogel L;Matsuoka Y;Lindsley WG;Jin H;Subbarao K

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甲型流感大流行和流行性流感病毒的流行病学成功有赖于通过呼吸道飞沫在人与人之间有效传播的能力。流感病毒的呼吸道飞沫(RD)传播需要有效复制传染性流感粒子并将其释放到空气中。2009年大流行H1N1(PH1N1)病毒起源于北美三重配猪(TRS)病毒与欧亚猪病毒的重新组合,后者提供神经氨酸酶(NA)和M基因片段。TRS和欧亚猪病毒都会在人类中造成零星感染,但与PH1N1病毒不同,它们没有在人与人之间传播。我们在雪貂模型中评估了PH1N1及其前体病毒,以确定不同的病毒基因片段对流感病毒颗粒释放到空气中的贡献以及对PH1N1病毒传播性的贡献。我们发现,欧亚起源的基因片段有助于PH1N1病毒的有效RD传播,可能是通过调节含有流感病毒RNA的颗粒释放到空气中。所有病毒在受感染雪貂的上呼吸道复制良好,表明病毒复制以外的因素对流感病毒颗粒的释放和传播非常重要。我们的研究表明,含有流感病毒RNA的颗粒释放到空气中与NA活性增加相关。此外,PH1N1病毒的多形性表型依赖于欧亚起源的基因片段,这表明传播和病毒形态之间存在联系。我们已经证明,病毒被不同程度地释放到呼出的空气中,一系列基因影响着PH1N1病毒的传播性。甲型流感病毒通过呼吸道飞沫在人与人之间迅速传播。在这项研究中,我们使用雪貂模型来探索病毒在流感病毒RD传播中的作用。2009年大流行H1N1(PH1N1)病毒起源于北美三重配猪(TRS)病毒与欧亚猪病毒的重新组合。TRS和欧亚猪病毒此前都曾在人类中引起零星感染,但与PH1N1病毒不同,它们未能在人与人之间传播。我们评估了含有流感病毒的气溶胶的释放以及PH1N1、TRS和欧亚病毒在雪貂中的传播性,发现欧亚起源的基因片段通过调节含有流感病毒RNA的颗粒的释放而促进了PH1N1病毒的有效RD传播。含有病毒RNA的颗粒的释放增加与病毒神经氨酸酶活性和丝状病毒颗粒的产生增加有关。这些观察结果加强了我们目前对流感病毒RD传播的病毒需求的了解,并对评估新型流感病毒传播的潜力有意义。
The epidemiological success of pandemic and epidemic influenza A viruses relies on the ability to transmit efficiently from person-to-person via respiratory droplets. Respiratory droplet (RD) transmission of influenza viruses requires efficient replication and release of infectious influenza particles into the air. The 2009 pandemic H1N1 (pH1N1) virus originated by reassortment of a North American triple reassortant swine (TRS) virus with a Eurasian swine virus that contributed the neuraminidase (NA) and M gene segments. Both the TRS and Eurasian swine viruses caused sporadic infections in humans, but failed to spread from person-to-person, unlike the pH1N1 virus. We evaluated the pH1N1 and its precursor viruses in a ferret model to determine the contribution of different viral gene segments on the release of influenza virus particles into the air and on the transmissibility of the pH1N1 virus. We found that the Eurasian-origin gene segments contributed to efficient RD transmission of the pH1N1 virus likely by modulating the release of influenza viral RNA-containing particles into the air. All viruses replicated well in the upper respiratory tract of infected ferrets, suggesting that factors other than viral replication are important for the release of influenza virus particles and transmission. Our studies demonstrate that the release of influenza viral RNA-containing particles into the air correlates with increased NA activity. Additionally, the pleomorphic phenotype of the pH1N1 virus is dependent upon the Eurasian-origin gene segments, suggesting a link between transmission and virus morphology. We have demonstrated that the viruses are released into exhaled air to varying degrees and a constellation of genes influences the transmissibility of the pH1N1 virus. Influenza A viruses spread rapidly from person-to-person via respiratory droplets (RDs). In this study we used a ferret model to explore viral functions involved in RD transmission of influenza viruses. The 2009 pandemic H1N1 (pH1N1) virus originated by reassortment of a North American triple reassortant swine (TRS) virus with a Eurasian swine virus. Both TRS and Eurasian swine viruses had previously caused sporadic infections in humans, but failed to spread from person-to-person, unlike the pH1N1 virus. We evaluated the release of influenza virus-containing aerosols and the transmissibility of the pH1N1, TRS, and Eurasian viruses in ferrets and found that the Eurasian-origin gene segments contributed to efficient RD transmission of the pH1N1 virus by modulating the release of influenza viral RNA-containing particles into the air. The increased release of viral RNA-containing particles correlated with increased viral neuraminidase activity and production of filamentous viral particles. These observations enhance what we currently know about the viral requirements for influenza virus RD transmission and have implications for assessing the potential of novel influenza viruses to spread.
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