The differentiated airway epithelium infected by influenza viruses maintains the barrier function despite a dramatic loss of ciliated cells.
The differentiated airway epithelium infected by influenza viruses maintains the barrier function despite a dramatic loss of ciliated cells.
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DOI：
10.1038/srep39668
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发表时间：
2016-12-22
影响因子：
4.6
通讯作者：
Herrler G
中科院分区：
文献类型：
--
作者：
Wu NH;Yang W;Beineke A;Dijkman R;Matrosovich M;Baumgärtner W;Thiel V;Valentin-Weigand P;Meng F;Herrler G
在长期流感病毒感染期间，呼吸道上皮中的病毒-宿主相互作用尚未得到很好的表征。因此，我们建立了一个气-液界面培养系统的分化猪呼吸道上皮细胞研究病毒诱导的细胞损伤的影响。在我们的分化良好的细胞中，α 2，6-连接唾液酸主要表达在顶端表面，基底细胞主要表达α 2，3-连接唾液酸。在整个感染过程中，感染性病毒的释放维持在高滴度超过7天。受感染的上皮细胞发生凋亡，导致纤毛细胞的损失以及厚度变薄。然而，气道上皮细胞保持跨上皮电阻，并保留其屏障功能。纤毛细胞的损失由含有KRT 5基底细胞标记物但尚未分化成纤毛细胞的细胞补偿。这些特化的细胞在顶端表面显示α 2，3-连接的唾液酸增加。总之，我们的结果有助于解释流感病毒对气道上皮的局部感染。上皮细胞中粘膜纤毛清除的损害提供了一个解释，为什么先前的病毒感染使宿主更容易受到另一种病原体的继发性共感染。
Virus-host interactions in the respiratory epithelium during long term influenza virus infection are not well characterized. Therefore, we developed an air-liquid interface culture system for differentiated porcine respiratory epithelial cells to study the effect of virus-induced cellular damage. In our well-differentiated cells, α2,6-linked sialic acid is predominantly expressed on the apical surface and the basal cells mainly express α2,3-linked sialic acid. During the whole infection period, release of infectious virus was maintained at a high titre for more than seven days. The infected epithelial cells were subject to apoptosis resulting in the loss of ciliated cells together with a thinner thickness. Nevertheless, the airway epithelium maintained trans-epithelial electrical resistance and retained its barrier function. The loss of ciliated cells was compensated by the cells which contained the KRT5 basal cell marker but were not yet differentiated into ciliated cells. These specialized cells showed an increase of α2,3-linked sialic acid on the apical surface. In sum, our results help to explain the localized infection of the airway epithelium by influenza viruses. The impairment of mucociliary clearance in the epithelial cells provides an explanation why prior viral infection renders the host more susceptible to secondary co-infection by another pathogen.
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影响因子：
4.8
作者：
Cohen M;Zhang XQ;Senaati HP;Chen HW;Varki NM;Schooley RT;Gagneux P
通讯作者：
Gagneux P
影响因子：
5.4
作者：
Shin DL;Hatesuer B;Bergmann S;Nedelko T;Schughart K
通讯作者：
Schughart K
支气管上皮细胞中的流感H5N1和H1N1病毒复制和先天免疫反应受分化状态的影响。
影响因子：
3.7
作者：
Chan RW;Yuen KM;Yu WC;Ho CC;Nicholls JM;Peiris JS;Chan MC
通讯作者：
Chan MC
影响因子：
4.4
作者：
Meng, Fandan;Punyadarsaniya, Darsaniya;Herrler, Georg
通讯作者：
Herrler, Georg
影响因子：
5.4
作者：
Matrosovich, MN;Matrosovich, TY;Klenk, HD
通讯作者：
Klenk, HD