Human coronaviruses 229E and OC43 replicate and induce distinct antiviral responses in differentiated primary human bronchial epithelial cells
Human coronaviruses 229E and OC43 replicate and induce distinct antiviral responses in differentiated primary human bronchial epithelial cells
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DOI：
10.1152/ajplung.00374.2020
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发表时间：
2020-12-01
影响因子：
4.9
通讯作者：
Bartlett, Nathan W.
中科院分区：
文献类型：
--
作者：
Loo, Su-Ling;Wark, Peter A. B.;Bartlett, Nathan W.
新的致病性冠状病毒(CoVS)严重急性呼吸综合征冠状病毒1型(SARS-CoV-1；2002)、中东呼吸综合征(MERS)冠状病毒(MERS)-CoV(2012)和最近的SARS-CoV-2(2019年)的反复出现突显了需要提供生理信息的呼吸道上皮细胞感染模型来研究对CoV的免疫和抗病毒治疗的开发。为了解决这一问题，我们建立了两种人类冠状病毒的体外感染模型：甲型冠状病毒229E-CoV(229E)和乙型冠状病毒OC43-CoV(OC43)。在气液界面(ALI)培养原代BEC，用229E或OC43感染BEC，检测天然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，但表现出不同的复制动力学：229E复制迅速，病毒载量在感染后24 h达到高峰，而OC43复制较慢，在感染后96 h达到高峰。这与不同的抗病毒反应谱有关，与OC43感染时没有天然免疫激活相比，229E时I/III型干扰素和干扰素刺激基因(ISGs)的表达增加。了解先前已建立的冠状病毒的宿主与病毒的相互作用将有助于深入了解SARS-CoV-2诱导的呼吸道疾病和其他未来可能由人畜共患病来源的冠状病毒的致病机制。
The recurrent emergence of novel, pathogenic coronaviruses (CoVs) severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; 2002), Middle East respiratory syndrome (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 antiviral 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 h postinfection, while OC43 replication was slower peaking at 96 h after infection. This was associated with diverse antiviral response profiles defined by increased expression of type I/III interferons and interferon-stimulated genes (ISGs) by 229E compared with no innate immune activation with OC43 infection. 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.