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Viral co-infection of differentiated airway cells pre-infected by influenza viruses

流感病毒预感染的分化气道细胞的病毒共感染

基本信息

批准号：
329248398
负责人：
Professor Dr. Georg Herrler
金额：
--
依托单位：
Institut für Virologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2017
资助国家：
德国
起止时间：
2016-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/329248398?language=en
关键词：
Viral co infection differentiated airway

项目摘要

After infection of the airways, in both human and animal specimen, often more than one infectious agent is detected. Secondary infections may result in a more severe course of the disease. The molecular interactions between the pathogens and the host during co-infection are not well characterized. To apply an in vitro model which mimics the in vivo situation as closely as possible, we have established an air-liquid interface culture system for porcine airway epithelial cells and used it to analyze the infection of differentiated respiratory epithelial cells by influenza viruses. Infection resulted in the loss of ciliated cells. The loss was compensated by basal cells that differentiated into specialized cells. These cells maintain the barrier function of the epithelium; however, for a longer time period they do not contain cilia and during this time, they cannot contribute to the mucociliary clearance system. Furhermore, these cells differ from ciliated cells in the expression pattern of surface proteins. Based on these findings we hypothesize that during the regeneration, the foci of infection have an increased susceptibility to infection by secondary pathogens. In the proposed project we will analyse whether airway eptihelial cells infected by influenza viruses show an increased susceptibility to infection by secondary pathogens. With respect to secondary pathogens, we will focus on viruses. In the first stage of the project, we will apply different methods to characterize changes in the expression pattern of surface proteins during regeneration after an infection by influenza viruses. Our special focus will be on a virus receptor, porcine amonopeptidase N (pAPN), the cellular receptor for porcine respiratory coronavirus (PRCoV). In the following chapter, we will analyse how a prior infection by influenza viruses affects the subsequent infection by PRCoV. The second model virus is porcine reproductive and respiratory syndrome virus (PRRSV). This virus uses macrophages as primary target cells. We will determine to what extent the adherence of PRRSV-infected macrophages to the airway epithelium is increased after an infection by influenza viruses; furthermore, we will analyse whether the adhering macrophages are able to transmit the PRRSV infection across the barrier of the airway epithelium. Finally, we will determine whether the results obtained with porcine airway cells are valid also for human respiratory epithelial cells. The results of this project will reveal to what extent prior infection by influenza viruses facilitates infection by secondary viral infection. In this way, we will increase the knowledge about the interactions between pathogens and the host during co-infections.

在人类和动物样本中，在呼吸道感染后，通常检测到一种以上的传染性病原体。继发性感染可能导致疾病的更严重过程。在共感染过程中病原体和宿主之间的分子相互作用还没有得到很好的表征。为了应用尽可能模拟体内情况的体外模型，我们建立了猪气道上皮细胞的气-液界面培养系统，并用它来分析流感病毒对分化的呼吸道上皮细胞的感染。感染导致纤毛细胞的损失。这种损失由分化成特化细胞的基底细胞补偿。这些细胞维持上皮的屏障功能;然而，在较长的时间段内，它们不含纤毛，并且在此期间，它们不能有助于粘膜纤毛清除系统。此外，这些细胞的表面蛋白的表达模式不同于纤毛细胞。基于这些发现，我们推测，在再生过程中，感染病灶对继发性病原体感染的易感性增加。在拟议的项目中，我们将分析是否被流感病毒感染的气道上皮细胞显示出对继发性病原体感染的易感性增加。关于次要病原体，我们将重点关注病毒。在项目的第一阶段，我们将采用不同的方法来表征流感病毒感染后再生过程中表面蛋白表达模式的变化。我们将特别关注病毒受体，猪氨肽酶N（pAPN），猪呼吸道冠状病毒（PRCoV）的细胞受体。在下一章中，我们将分析先前感染流感病毒如何影响随后感染PRCoV。第二种模式病毒是猪繁殖与呼吸综合征病毒（PRRSV）。这种病毒使用巨噬细胞作为主要靶细胞。我们将确定在流感病毒感染后，PRRSV感染的巨噬细胞对气道上皮的粘附增加到何种程度;此外，我们将分析粘附的巨噬细胞是否能够穿过气道上皮的屏障传播PRRSV感染。最后，我们将确定用猪气道细胞获得的结果是否也适用于人呼吸道上皮细胞。该项目的结果将揭示先前感染流感病毒在多大程度上促进了继发性病毒感染。通过这种方式，我们将增加关于病原体和宿主在合并感染期间相互作用的知识。