The recurrent emergence of novel, pathogenic coronaviruses (CoVs) SARS-CoV-1 (2002), MERS-CoV (2012) and most recently SARS-CoV-2 (2019) has highlighted the need for physiologically informative airway epithelial cell infection models for studying immunity to CoVs and development of anti-viral therapies. To address this, we developed an in-vitro infection model for two human coronaviruses; alphacoronavirus 229E-CoV (229E) and betacoronavirus OC43-CoV (OC43) in differentiated primary human bronchial epithelial cells (pBECs). Primary BECs from healthy subjects were grown at air liquid interface (ALI) and infected with 229E or OC43, and replication kinetics and time-course expression of innate immune mediators were assessed. OC43 and 229E-CoVs replicated in differentiated pBECs but displayed distinct replication kinetics: 229E replicated rapidly with viral load peaking at 24 hours post-infection, whilst OC43 replication was slower peaking at 7 days after infection. This was associated with diverse anti-viral response profiles defined by increased expression of type I/III interferons and interferon-stimulated genes (ISGs) by 229E compared to OC43. Understanding the host-virus interaction for previously established coronaviruses will give insight into pathogenic mechanisms underpinning SARS-CoV-2-induced respiratory disease and other future coronaviruses that may arise from zoonotic sources.

中文翻译：

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人类冠状病毒229E和OC43在分化的人类支气管上皮细胞中复制并诱导不同的抗病毒反应。

新型的致病性冠状病毒（CoV）SARS-CoV-1（2002），MERS-CoV（2012）和最近的SARS-CoV-2（2019）的反复出现凸显了需要生理学上有用的气道上皮细胞感染模型研究CoV的免疫力和抗病毒疗法的发展。为了解决这个问题，我们开发了两种人类冠状病毒的体外感染模型。α冠状病毒229E-CoV（229E）和β冠状病毒OC43-CoV（OC43）在分化的人支气管上皮细胞（pBEC）中。健康受试者的原代BEC在气液界面（ALI）上生长并感染229E或OC43，并评估了先天免疫介质的复制动力学和时程表达。OC43和229E-CoV在分化的pBEC中复制，但显示出不同的复制动力学：229E快速复制，在感染后24小时病毒载量达到峰值，而OC43复制在感染后7天达到峰值。与OC43相比，这与通过229E增加I / III型干扰素和干扰素刺激基因（ISG）的表达所定义的多种抗病毒反应谱有关。了解以前建立的冠状病毒的宿主病毒相互作用将深入了解SARS-CoV-2诱导的呼吸道疾病以及其他可能由人畜共患病源引起的未来冠状病毒的致病机制。与OC43相比，这与通过229E增加I / III型干扰素和干扰素刺激基因（ISG）的表达所定义的多种抗病毒反应谱有关。了解先前建立的冠状病毒的宿主-病毒相互作用将深入了解SARS-CoV-2诱导的呼吸道疾病和其他可能由人畜共患病源引起的未来冠状病毒的致病机制。与OC43相比，这与通过229E增加I / III型干扰素和干扰素刺激基因（ISG）的表达所定义的多种抗病毒反应谱有关。了解先前建立的冠状病毒的宿主-病毒相互作用将深入了解SARS-CoV-2诱导的呼吸道疾病和其他可能由人畜共患病源引起的未来冠状病毒的致病机制。