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从人类中分离出的猪源 H1 流感病毒在气溶胶状态下具有持续的感染性。

Swine-Origin H1 Influenza Viruses Isolated from Humans Exhibit Sustained Infectivity in an Aerosol State.

机构信息

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

出版信息

Appl Environ Microbiol. 2019 May 2;85(10). doi: 10.1128/AEM.00210-19. Print 2019 May 15.

Abstract

The relative importance of influenza virus transmission via aerosols is not fully understood, but experimental data suggest that aerosol transmission may represent a critical mode of influenza virus spread among humans. Decades ago, prototypical laboratory strains of influenza were shown to persist in aerosols; however, there is a paucity of data available covering currently circulating influenza viruses, which differ significantly from their predecessors. In this study, we evaluated the longevity of influenza viruses in aerosols generated in the laboratory. We selected a panel of H1 viruses that exhibit diverse transmission profiles in the ferret model, including four human isolates of swine origin (referred to as variant) and a seasonal strain. By measuring the ratio of viral RNA to infectious virus maintained in aerosols over time, we show that influenza viruses known to transmit efficiently through the air display enhanced stability in an aerosol state for prolonged periods compared to those viruses that do not transmit as efficiently. We then assessed whether H1 influenza virus was still capable of infecting and causing disease in ferrets after being aged in suspended aerosols. Ferrets exposed to very low levels of influenza virus (≤17 PFU) in aerosols aged for 15 or 30 min became infected, with five of six ferrets shedding virus in nasal washes at titers on par with ferrets who inhaled higher doses of unaged influenza virus. We describe here an underreported characteristic of influenza viruses, stability in aerosols, and make a direct connection to the role this characteristic plays in influenza transmission. Each time a swine influenza virus transmits to a human, it provides an opportunity for the virus to acquire adaptations needed for sustained human-to-human transmission. Here, we use aerobiology techniques to test the stability of swine-origin H1 subtype viruses in aerosols and evaluate their infectivity in ferrets. Our results show that highly transmissible influenza viruses display enhanced stability in an aerosol state compared to viruses that do not transmit as efficiently. Similar to human-adapted strains, swine-origin influenza viruses are infectious in ferrets at low doses even after prolonged suspension in the air. These data underscore the risk of airborne swine-origin influenza viruses and support the need for continued surveillance and refinement of innovative laboratory methods to investigate mammalian exposure to inhaled pathogens. Determination of the molecular markers that affect the longevity of airborne influenza viruses will improve our ability to quickly identify emerging strains that present the greatest threat to public health.

摘要

病毒通过气溶胶传播的相对重要性尚不完全清楚,但实验数据表明,气溶胶传播可能是流感病毒在人群中传播的一种关键模式。几十年前,已证明原型实验室株流感病毒可在气溶胶中持续存在;然而,目前关于流行的流感病毒的数据很少,这些病毒与它们的前身有很大的不同。在这项研究中,我们评估了实验室产生的气溶胶中流感病毒的寿命。我们选择了一组在雪貂模型中表现出不同传播特征的 H1 病毒,包括四种源自猪的人类分离株(称为变体)和一种季节性株。通过测量气溶胶中病毒 RNA 与传染性病毒随时间保持的比例,我们表明,与传播效率较低的病毒相比,通过空气高效传播的流感病毒在气溶胶状态下具有更长时间的增强稳定性。然后,我们评估了在悬浮气溶胶中老化后,H1 流感病毒是否仍能够感染和引起雪貂发病。暴露于气溶胶中非常低水平(≤17 PFU)流感病毒的雪貂会被感染,其中 6 只中的 5 只在鼻冲洗液中排出病毒,病毒滴度与吸入未老化流感病毒更高剂量的雪貂相当。我们在这里描述了流感病毒的一个未被报道的特征,即气溶胶中的稳定性,并直接将这一特征与它在流感传播中的作用联系起来。每次猪流感病毒传播给人类,都会为病毒提供获得持续人际传播所需适应的机会。在这里,我们使用空气生物学技术来测试源自猪的 H1 亚型病毒在气溶胶中的稳定性,并评估它们在雪貂中的感染性。我们的结果表明,与传播效率较低的病毒相比,高传染性流感病毒在气溶胶状态下显示出增强的稳定性。与适应人类的株一样,即使在长时间悬浮在空气中后,源自猪的流感病毒在低剂量下也可在雪貂中感染。这些数据强调了空气传播的源自猪的流感病毒的风险,并支持继续进行监测和改进创新的实验室方法,以研究哺乳动物对吸入病原体的暴露。确定影响空气传播流感病毒寿命的分子标记将提高我们快速识别对公共卫生构成最大威胁的新兴株的能力。

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