Differentiated human airway organoids to assess infectivity of emerging influenza virus

Zhou, Jie; Li, Cun; Sachs, Norman; Chiu, Man Chun; Wong, Bosco Ho-Yin; Chu, Hin; Poon, Vincent Kwok-Man; Wang, Dong; Zhao, Xiaoyu; Wen, Lei; Song, Wenjun; Yuan, Shuofeng; Wong, Kenneth Kak-Yuen; Chan, Jasper Fuk-Woo; To, Kelvin Kai-Wang; Chen, Honglin; Clevers, Hans; Yuen, Kwok-Yung

To verify the ability of 2D PD organoids to assess the zoonotic potential of animal viruses and identify the human-infective virus, we compared the relative replication capacities of H7N9/Ah and H7N2 viruses and of another pair of viruses, the highly human-infective H1N1pdm and a swine H1N1 isolate (H1N1sw). The higher replicative capacity of H7N9/Ah over H7N2 virus was more pronounced in the 2D PD organoids than in the 3D PD organoids; the viral titer of H7N9/Ah in the apical medium was 3-4 log 10 units higher than that of the H7N2 virus (Fig. 5B) . Consistently, H1N1pdm replicated dramatically, with a viral titer in the apical medium 1-2 log 10 units higher than that of H1N1sw. Due to the epithelial barrier formed in the 2D monolayers and the preferential release of virus from the cell apical side, the viral titers in the basolateral medium were consistently lower than those in apical medium at the corresponding time points. Nevertheless, the differences in replicative capacity between H7N9/ Ah versus H7N2 and H1N1pdm versus H1N1sw were even more prominent in basal medium than in apical medium at most time points.