Wark Peter A B, Grissell Terry, Davies Bronwyn, See Hayley, Gibson Peter G
Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, UK.
Respirology. 2009 Mar;14(2):180-6. doi: 10.1111/j.1440-1843.2009.01480.x. Epub 2009 Feb 4.
Infection with rhinovirus (RV) is the most common trigger for acute asthma and COPD. The aim of this study was to characterize the variability in the response of primary bronchial epithelial cells to infection with several strains of RV.
RV strains, RV-43, RV-48 (major group RV), RV-47 (minor) and EV-68 (enterovirus), were cultured from subjects with acute asthma and compared with the laboratory RV strains, RV-16, RV-14 (major) and RV-1B (minor). Primary bronchial epithelial cells were obtained from healthy control and asthmatic subjects by endobronchial brushing. Response to infection was assessed by the release of IL-6, interferon (IFN)-gamma induced protein (IP)-10 and IFN-beta, as measured by ELISA. Viral replication was assessed by serial titration assays and cell viability by flow cytometry.
Major group RV strains and EV-68 all efficiently infected and replicated in epithelial cells causing little cell death. The clinical major group RV strains caused greater release of IL-6 and IP-10 compared with laboratory major group RV strains. Infection with minor group RV resulted in greater release of IP-10, IL-6 and IFN-beta that was associated with induction of apoptosis and less efficient viral replication. Asthmatic bronchial epithelial cells were less able to respond by releasing IFN-beta following infection with RV-1B.
Considerable diversity exists in the response to RV strains, especially between minor and major group RV. The impaired IFN-beta response in asthmatic bronchial epithelial cells may make them particularly susceptible to minor group RV.
鼻病毒(RV)感染是急性哮喘和慢性阻塞性肺疾病(COPD)最常见的诱因。本研究的目的是描述几种RV毒株感染后原代支气管上皮细胞反应的变异性。
从急性哮喘患者中培养出RV毒株RV-43、RV-48(主要组RV)、RV-47(次要组)和肠道病毒68型(EV-68),并与实验室RV毒株RV-16、RV-14(主要组)和RV-1B(次要组)进行比较。通过支气管内刷检从健康对照者和哮喘患者中获取原代支气管上皮细胞。通过酶联免疫吸附测定(ELISA)检测白细胞介素-6(IL-6)、干扰素(IFN)-γ诱导蛋白(IP)-10和IFN-β的释放来评估对感染的反应。通过系列滴定试验评估病毒复制情况,通过流式细胞术评估细胞活力。
主要组RV毒株和EV-68均能有效感染上皮细胞并在其中复制,几乎不引起细胞死亡。与实验室主要组RV毒株相比,临床主要组RV毒株导致IL-6和IP-10的释放量更大。次要组RV感染导致IP-10、IL-6和IFN-β的释放量更大,这与细胞凋亡的诱导有关,且病毒复制效率较低。哮喘支气管上皮细胞在感染RV-1B后释放IFN-β的反应能力较弱。
对RV毒株的反应存在相当大的差异,尤其是在次要组和主要组RV之间。哮喘支气管上皮细胞中IFN-β反应受损可能使其对次要组RV特别易感。