Rhinovirus C targets ciliated airway epithelial cells.
Rhinovirus C targets ciliated airway epithelial cells.
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DOI：
10.1186/s12931-017-0567-0
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发表时间：
2017-05-04
影响因子：
5.8
通讯作者：
Gern JE
中科院分区：
文献类型：
--
作者：
Griggs TF;Bochkov YA;Basnet S;Pasic TR;Brockman-Schneider RA;Palmenberg AC;Gern JE
2006年首次发现的鼻病毒C （RV-C）在儿童和哮喘患者中产生很高的症状负担，然而，其主要靶宿主细胞在气道中仍不清楚。我们的主要假设是RV-C靶向纤毛气道上皮细胞（AECs），并且细胞特异性是由唯一已知的RV-C细胞进入因子，钙粘蛋白相关家族成员3 （CDHR3）的限制性和高表达决定的。采用免疫荧光和延时荧光成像技术评估人支气管上皮细胞（HBEC）培养物中RV-C15 （C15）的感染情况。采用免疫组化方法评价c15感染的aec的形态。C15呈分散感染，感染细胞从上皮脱落。根据细胞培养条件的不同，感染C15的细胞百分比从1.4到14.7%不等。感染细胞的纤毛细胞标记物（乙酰化α -微管蛋白[aat]， p < 0.001）染色增加，但杯状细胞标记物（小麦胚芽凝集素或Muc5AC， p = ns）染色增加。CDHR3在纤毛上皮细胞中表达升高，而在其他上皮细胞中表达不升高（p < 0.01）。C15感染导致表达CDHR3的纤毛细胞减少27.4% （p < 0.01）。在AECs分化过程中，CDHR3表达逐渐增加，并与RV-C结合和复制相关。RV-C仅在体外纤毛aec中复制，导致受感染的细胞脱落。CDHR3的表达与RV-C的结合和复制呈正相关，并且主要局限于纤毛aec。我们的数据表明，调节分化和CDHR3产生的因素可能是RV-C疾病严重程度的重要决定因素。本文的在线版本（doi:10.1186/s12931-017-0567-0）包含补充材料，可供授权用户使用。
The Rhinovirus C (RV-C), first identified in 2006, produce high symptom burdens in children and asthmatics, however, their primary target host cell in the airways remains unknown. Our primary hypotheses were that RV-C target ciliated airway epithelial cells (AECs), and that cell specificity is determined by restricted and high expression of the only known RV-C cell-entry factor, cadherin related family member 3 (CDHR3). RV-C15 (C15) infection in differentiated human bronchial epithelial cell (HBEC) cultures was assessed using immunofluorescent and time-lapse epifluorescent imaging. Morphology of C15-infected differentiated AECs was assessed by immunohistochemistry. C15 produced a scattered pattern of infection, and infected cells were shed from the epithelium. The percentage of cells infected with C15 varied from 1.4 to 14.7% depending on cell culture conditions. Infected cells had increased staining for markers of ciliated cells (acetylated-alpha-tubulin [aat], p < 0.001) but not markers of goblet cells (wheat germ agglutinin or Muc5AC, p = ns). CDHR3 expression was increased on ciliated epithelial cells, but not other epithelial cells (p < 0.01). C15 infection caused a 27.4% reduction of ciliated cells expressing CDHR3 (p < 0.01). During differentiation of AECs, CDHR3 expression progressively increased and correlated with both RV-C binding and replication. The RV-C only replicate in ciliated AECs in vitro, leading to infected cell shedding. CDHR3 expression positively correlates with RV-C binding and replication, and is largely confined to ciliated AECs. Our data imply that factors regulating differentiation and CDHR3 production may be important determinants of RV-C illness severity. The online version of this article (doi:10.1186/s12931-017-0567-0) contains supplementary material, which is available to authorized users.