Characterization of Nipah virus infection in a model of human airway epithelial cells cultured at an air-liquid interface
Characterization of Nipah virus infection in a model of human airway epithelial cells cultured at an air-liquid interface
复制标题
DOI：
10.1099/jgv.0.000441
复制
发表时间：
2016-05-01
影响因子：
3.8
通讯作者：
Rockx, Barry
中科院分区：
文献类型：
--
作者：
Escaffre, Olivier;Borisevich, Viktoriya;Rockx, Barry
尼帕病毒(Nipah Virus，NIV)是一种新出现的副粘病毒，可导致人类致命的呼吸道疾病。目前还没有疫苗/治疗药物被批准用于人类。此前报告的人与人之间的传播是在疫情期间发生的，新城疫病毒可以从呼吸道分泌物中分离出来，但马来西亚出现呼吸道症状的病例比例明显低于孟加拉国。此前，我们发现原代人类呼吸道基底上皮细胞对新城疫病毒马来西亚(M)株和孟加拉国(B)株都敏感，导致强烈的促炎反应。然而，新城疫病毒靶标的人呼吸道上皮细胞及其在新城疫病毒传播和新城疫病毒相关肺部发病机制中的作用仍不清楚。在这里，我们使用在气液界面培养的人气管/支气管(B-ALI)和小气道(S-ALI)上皮的模型来表征新城疫病毒对人类呼吸道上皮的感染。我们发现NIV-M和NIV-B感染B/S-ALI的纤毛细胞和分泌细胞，S-ALI而不是B-ALI的感染导致了上皮完整性的破坏和宿主对人类免疫细胞的反应。有趣的是，Niv-B在B-ALI中的复制效率比Niv-M更高。这些结果表明，人的气管/支气管上皮有利于新城疫病毒的复制和脱落，同时诱导有限的宿主反应。我们的数据表明，小气道上皮容易发炎和损伤，并构成病毒进入肺血管系统的一个点。使用相关的人类呼吸道模型，如B/S-ALI，对于理解新城疫相关的肺部发病机制和确定允许人传人的潜在机制至关重要。
Nipah virus (NiV) is an emerging paramyxovirus that can cause lethal respiratory illness in humans. No vaccine/therapeutic is currently licensed for humans. Human-to-human transmission was previously reported during outbreaks and NiV could be isolated from respiratory secretions, but the proportion of cases in Malaysia exhibiting respiratory symptoms was significantly lower than that in Bangladesh. Previously, we showed that primary human basal respiratory epithelial cells are susceptible to both NiV-Malaysia (M) and -Bangladesh (B) strains causing robust pro-inflammatory responses. However, the cells of the human respiratory epithelium that NiV targets are unknown and their role in NiV transmission and NiV-related lung pathogenesis is still poorly understood. Here, we characterized NiV infection of the human respiratory epithelium using a model of the human tracheal/bronchial (B-ALI) and small airway (S-ALI) epithelium cultured at an air-liquid interface. We show that NiV-M and NiV-B infect ciliated and secretory cells in B/S-ALI, and that infection of S-ALI, but not B-ALI, results in disruption of the epithelium integrity and host responses recruiting human immune cells. Interestingly, NiV-B replicated more efficiently in B-ALI than did NiV-M. These results suggest that the human tracheal/bronchial epithelium is favourable to NiV replication and shedding, while inducing a limited host response. Our data suggest that the small airways epithelium is prone to inflammation and lesions as well as constituting a point of virus entry into the pulmonary vasculature. The use of relevant models of the human respiratory tract, such as B/S-ALI, is critical for understanding NiV-related lung pathogenesis and identifying the underlying mechanisms allowing human-to-human transmission.