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Differentiated human airway organoids to assess infectivity of emerging influenza virus

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  • Differentiated human airway organoids to assess infectivity of emerging influenza virus

    Proc Natl Acad Sci U S A. 2018 Jun 11. pii: 201806308. doi: 10.1073/pnas.1806308115. [Epub ahead of print]
    Differentiated human airway organoids to assess infectivity of emerging influenza virus.

    Zhou J1,2,3, Li C2, Sachs N4, Chiu MC2, Wong BH2, Chu H1,2,3, Poon VK2, Wang D2, Zhao X2, Wen L2, Song W2,5, Yuan S2, Wong KK6, Chan JF1,2,3,7,8, To KK1,2,3,7,8, Chen H1,2,3, Clevers H9,10, Yuen KY11,2,3,7,8.
    Author information

    Abstract

    Novel reassortant avian influenza H7N9 virus and pandemic 2009 H1N1 (H1N1pdm) virus cause human infections, while avian H7N2 and swine H1N1 virus mainly infect birds and pigs, respectively. There is no robust in vitro model for assessing the infectivity of emerging viruses in humans. Based on a recently established method, we generated long-term expanding 3D human airway organoids which accommodate four types of airway epithelial cells: ciliated, goblet, club, and basal cells. We report differentiation conditions which increase ciliated cell numbers to a nearly physiological level with synchronously beating cilia readily discernible in every organoid. In addition, the differentiation conditions induce elevated levels of serine proteases, which are essential for productive infection of human influenza viruses and low-pathogenic avian influenza viruses. We also established improved 2D monolayer culture conditions for the differentiated airway organoids. To demonstrate the ability of differentiated airway organoids to identify human-infective virus, 3D and 2D differentiated airway organoids are applied to evaluate two pairs of viruses with known distinct infectivity in humans, H7N9/Ah versus H7N2 and H1N1pdm versus an H1N1 strain isolated from swine (H1N1sw). The human-infective H7N9/Ah virus replicated more robustly than the poorly human-infective H7N2 virus; the highly human-infective H1N1pdm virus replicated to a higher titer than the counterpart H1N1sw. Collectively, we developed differentiated human airway organoids which can morphologically and functionally simulate human airway epithelium. These differentiated airway organoids can be applied for rapid assessment of the infectivity of emerging respiratory viruses to human.


    KEYWORDS:

    airway organoid; infectivity; influenza virus; proximal differentiation

    PMID: 29891677 DOI: 10.1073/pnas.1806308115
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