Porcine Respiratory Coronavirus as a Model for Acute Respiratory Coronavirus Disease.

Porcine Respiratory Coronavirus as a Model for Acute Respiratory Coronavirus Disease.
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DOI:
10.3389/fimmu.2022.867707
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发表时间:
2022
影响因子:
7.3
通讯作者:
Tchilian E
Tchilian E
中科院分区:
医学2区
文献类型:
--
作者:
Keep S;Carr BV;Lean FZX;Fones A;Newman J;Dowgier G;Freimanis G;Vatzia E;Polo N;Everest H;Webb I;Mcnee A;Paudyal B;Thakur N;Nunez A;MacLoughlin R;Maier H;Hammond J;Bailey D;Waters R;Charleston B;Tuthill T;Britton P;Bickerton E;Tchilian E

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鉴于严重急性呼吸道综合征冠状病毒2型(SARS-CoV-2)的大流行,我们建立了猪呼吸道冠状病毒(PRCV)模型,用于深入评价这一重要病毒家族的致病机制、病毒学和免疫应答。猪是一种大型动物,具有与人类相似的生理学和免疫学,是PRCV的天然宿主。研究了四种PRCV菌株,并显示其诱导不同程度的肺病理学。重要的是,尽管所有四种毒株在体外猪细胞系和体内上呼吸道中复制得同样好,但引起更严重肺部病理的PRCV毒株也能够在离体气管器官培养物中以及在体内气管和肺中复制。研究了引起最严重肺部病理学的PRCV 135感染的时间过程。病毒从上呼吸道脱落,直到感染后第10天,呼吸道粘膜以及嗅觉和支持细胞感染,提供了一个很好的模型来研究上呼吸道疾病,除了通常已知的下呼吸道疾病PRCV。感染动物产生抗体和T细胞应答,与四种PRCV株和传染性胃肠炎病毒交叉反应。抗体反应在体外器官培养物中重现。将不同致病性PRCV感染猪的感染和免疫控制机制与来自SARS-CoV-2感染和我们体外器官培养的人类数据进行比较,将能够确定冠状病毒感染和疾病发病机制中的关键事件。
In the light of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we have developed a porcine respiratory coronavirus (PRCV) model for in depth mechanistic evaluation of the pathogenesis, virology and immune responses of this important family of viruses. Pigs are a large animal with similar physiology and immunology to humans and are a natural host for PRCV. Four PRCV strains were investigated and shown to induce different degrees of lung pathology. Importantly, although all four strains replicated equally well in porcine cell lines in vitro and in the upper respiratory tract in vivo, PRCV strains causing more severe lung pathology were also able to replicate in ex vivo tracheal organ cultures as well as in vivo in the trachea and lung. The time course of infection of PRCV 135, which caused the most severe pulmonary pathology, was investigated. Virus was shed from the upper respiratory tract until day 10 post infection, with infection of the respiratory mucosa, as well as olfactory and sustentacular cells, providing an excellent model to study upper respiratory tract disease in addition to the commonly known lower respiratory tract disease from PRCV. Infected animals made antibody and T cell responses that cross reacted with the four PRCV strains and Transmissible Gastroenteritis Virus. The antibody response was reproduced in vitro in organ cultures. Comparison of mechanisms of infection and immune control in pigs infected with PRCVs of differing pathogenicity with human data from SARS-CoV-2 infection and from our in vitro organ cultures, will enable key events in coronavirus infection and disease pathogenesis to be identified.
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发表时间: 1975-01-01
影响因子: 3.8
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发表时间: 2020-09-25
期刊: Science (New York, N.Y.)
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影响因子: 4.6
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发表时间: 1990-03-01
影响因子: 2.4
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DOI: 10.1016/0378-1135(79)90033-6
发表时间: 1979-01-01
影响因子: 3.3
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