Hui KPY, et al. - Experts compared the replication competence, tissue tropism, and host responses elicited by human and avian strains of influenza A virus in ex-vivo human bronchus and human airway organoids. Results that were comparable to those observed in human ex-vivo bronchus cultures were provided by the human airway organoid cultures. Therefore, an alternative physiologically relevant experimental model for investigating virus tropism and replication competence that could be utilized in evaluating the pandemic threat of animal influenza viruses was provided in the findings.

Methods

• Authors collected ex-vivo cultures of the human bronchus and cultured human airway organoids from lung stem cells that were obtained from human lung tissues removed as part of the routine clinical care of patients undergoing surgical resection.
• They compared viral replication competence, tissue tropism, and cytokine and chemokine induction of avian influenza A viruses isolated from humans (Sh2/H7N9, H5N1/483, H5N6/39715) and human H1N1pdm/415742 in airway organoids and ex-vivo bronchus explant cultures.

Results

• Human airway organoids, virus tropism, and replication kinetics of human and avian influenza A viruses mimicked those found in ex-vivo cultures of human bronchus explants.
• Replication to significantly higher titres was noted in both airway organoids and bronchus explants, influenza A H1N1 subtype (H1N1) and avian influenza A H7N9 viruses than the highly pathogenic avian influenza (HPAI) H5N1, whereas HPAI H5N6 replication was moderate.
• In both airway organoids and bronchus explants, H1N1, H7N9, and H5N6 viruses infected ciliated cells and goblet cells, but not basal cells.
• Findings suggested significantly higher expression of cytokines, interleukin 6, and interferon β, and the chemokine regulated-on-activation, normal T-cell expressed and secreted in human airway organoids infected with HPAI H5N1 virus than H1N1pdm/415742, Sh2/H7N9, and H5N6/39715 viruses.
• They noted significantly higher expression of monocyte chemoattractant protein-1 in human organoids infected with HPAI H5N1 virus than H1N1pdm/415742 and Sh2/H7N9 viruses.