School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region, China.
Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
J Infect Dis. 2022 Jan 5;225(1):65-74. doi: 10.1093/infdis/jiab286.
A(H1N1)pdm09 influenza viruses replicate efficiently in respiratory epithelia and are transmitted via respiratory droplets and aerosols expelled by infected hosts. The relative onward transmission potential of influenza viruses replicating in the upper and lower respiratory epithelial cells has not been fully defined.
Wild-type and barcoded A(H1N1)pdm09 viruses that differed by 2 synonymous mutations per gene segment were inoculated into ferrets via intranasal and intratracheal routes. Naive recipients were exposed to the exhaled breath of inoculated donors for 8 hours on day 2 postinoculation. Onward transmission potential of wild-type and barcoded genotypes were monitored by next generation sequencing.
Transmissible airborne particles were respired from the upper but not the lower respiratory epithelial cells of donor ferrets. There was limited mixing of viral populations replicating in the upper and lower respiratory tissues.
The ferret upper respiratory epithelium was mapped as the anatomic site that generated influenza virus-laden particles mediating onward transmission by air. Our results suggest that vaccines and antivirals should aim to reduce viral loads in the upper respiratory tract for prevention of influenza transmission.
A(H1N1)pdm09 流感病毒在呼吸道上皮细胞中高效复制，并通过受感染宿主排出的呼吸道飞沫和气溶胶传播。在呼吸道上下皮细胞中复制的流感病毒的相对传播潜力尚未完全确定。
通过鼻腔和气管内途径将野生型和带有条形码的 A(H1N1)pdm09 病毒接种到雪貂体内，这些病毒在每个基因片段中存在 2 个同义突变的差异。在接种后第 2 天，将未感染的接受者暴露于接种供体呼出的呼吸空气中 8 小时。通过下一代测序监测野生型和条形码基因型的传播潜力。
可传播的空气传播颗粒从供体雪貂的上呼吸道上皮细胞中呼出，但不从下呼吸道上皮细胞中呼出。在上呼吸道和下呼吸道组织中复制的病毒群体之间混合有限。
雪貂的上呼吸道上皮细胞被定位为产生携带流感病毒的颗粒的解剖部位，通过空气介导的传播。我们的研究结果表明，疫苗和抗病毒药物的目标应该是降低上呼吸道的病毒载量，以预防流感传播。
