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冠状病毒与人类气道:病毒-宿主相互作用研究的通用系统

Coronaviruses and the human airway: a universal system for virus-host interaction studies.

作者信息

Jonsdottir Hulda R, Dijkman Ronald

机构信息

Federal Department of Home Affairs, Institute of Virology and Immunology, Länggassstrasse 122, 3012, Bern, Switzerland.

Department of Infectious diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

出版信息

Virol J. 2016 Feb 6;13:24. doi: 10.1186/s12985-016-0479-5.

Abstract

Human coronaviruses (HCoVs) are large RNA viruses that infect the human respiratory tract. The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Various animal models have been established to investigate HCoV infection, including mice and non-human primates. To establish a link between the research conducted in animal models and humans, an organotypic human airway culture system, that recapitulates the human airway epithelium, has been developed. Currently, different cell culture systems are available to recapitulate the human airways, including the Air-Liquid Interface (ALI) human airway epithelium (HAE) model. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. These organotypic human airway cultures represent a universal platform to study respiratory virus-host interaction by offering more detailed insights compared to cell lines. Additionally, the epidemic potential of this virus family highlights the need for both vaccines and antivirals. No commercial vaccine is available but various effective antivirals have been identified, some with potential for human treatment. These morphological airway cultures are also well suited for the identification of antivirals, evaluation of compound toxicity and viral inhibition.

摘要

人类冠状病毒(HCoVs)是感染人类呼吸道的大型RNA病毒。严重急性呼吸综合征冠状病毒和中东呼吸综合征冠状病毒的出现,以及四种常见冠状病毒的年度流行,凸显了阐明这些病毒用于逃避宿主免疫反应、确定其嗜性以及鉴定抗病毒化合物的不同机制的重要性。已经建立了各种动物模型来研究HCoV感染,包括小鼠和非人灵长类动物。为了在动物模型研究和人类研究之间建立联系,已经开发了一种能够模拟人类气道上皮的器官型人类气道培养系统。目前,有不同的细胞培养系统可用于模拟人类气道,包括气液界面(ALI)人类气道上皮(HAE)模型。气管支气管HAE培养物模拟了人类呼吸道病毒的主要进入点,而肺泡模型则有助于阐明病毒感染和肺泡发病机制中涉及的机制。这些器官型人类气道培养物通过提供比细胞系更详细的见解,代表了一个研究呼吸道病毒与宿主相互作用的通用平台。此外,这个病毒家族的流行潜力凸显了对疫苗和抗病毒药物的需求。目前没有商业疫苗可用,但已经鉴定出了各种有效的抗病毒药物,其中一些具有用于人类治疗的潜力。这些形态学气道培养物也非常适合用于鉴定抗病毒药物、评估化合物毒性和病毒抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af8d/4744394/b880108cf12a/12985_2016_479_Fig1_HTML.jpg

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