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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)在金黄仓鼠中的发病机制与传播

Pathogenesis and transmission of SARS-CoV-2 in golden hamsters.

作者信息

Sia Sin Fun, Yan Li-Meng, Chin Alex W H, Fung Kevin, Choy Ka-Tim, Wong Alvina Y L, Kaewpreedee Prathanporn, Perera Ranawaka A P M, Poon Leo L M, Nicholls John M, Peiris Malik, Yen Hui-Ling

机构信息

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

出版信息

Nature. 2020 Jul;583(7818):834-838. doi: 10.1038/s41586-020-2342-5. Epub 2020 May 14.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus with high nucleotide identity to SARS-CoV and to SARS-related coronaviruses that have been detected in horseshoe bats, has spread across the world and had a global effect on healthcare systems and economies. A suitable small animal model is needed to support the development of vaccines and therapies. Here we report the pathogenesis and transmissibility of SARS-CoV-2 in golden (Syrian) hamsters (Mesocricetus auratus). Immunohistochemistry assay demonstrated the presence of viral antigens in nasal mucosa, bronchial epithelial cells and areas of lung consolidation on days 2 and 5 after inoculation with SARS-CoV-2, followed by rapid viral clearance and pneumocyte hyperplasia at 7 days after inoculation. We also found viral antigens in epithelial cells of the duodenum, and detected viral RNA in faeces. Notably, SARS-CoV-2 was transmitted efficiently from inoculated hamsters to naive hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was not as efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally infected hamsters showed apparent weight loss on days 6-7 post-inoculation or post-contact; all hamsters returned to their original weight within 14 days and developed neutralizing antibodies. Our results suggest that features associated with SARS-CoV-2 infection in golden hamsters resemble those found in humans with mild SARS-CoV-2 infections.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是一种与SARS-CoV以及在菊头蝠中检测到的SARS相关冠状病毒具有高度核苷酸同源性的新型冠状病毒,已在全球范围内传播,对医疗系统和经济产生了全球性影响。需要一种合适的小动物模型来支持疫苗和治疗方法的开发。在此,我们报告了SARS-CoV-2在金黄(叙利亚)仓鼠(Mesocricetus auratus)中的发病机制和传播性。免疫组织化学分析表明,在接种SARS-CoV-2后第2天和第5天,鼻黏膜、支气管上皮细胞和肺实变区域存在病毒抗原,随后在接种后7天病毒迅速清除,肺细胞增生。我们还在十二指肠上皮细胞中发现了病毒抗原,并在粪便中检测到病毒RNA。值得注意的是,SARS-CoV-2通过直接接触和气溶胶从接种的仓鼠高效传播至未感染的仓鼠。通过污染笼子中的污染物传播效率较低。尽管在接种仓鼠的鼻腔冲洗液中连续14天检测到病毒RNA,但传染期较短,且与传染性病毒的检测相关,而非病毒RNA。接种和自然感染的仓鼠在接种或接触后第6 - 7天出现明显体重减轻;所有仓鼠在14天内恢复到原始体重并产生中和抗体。我们的结果表明,金黄仓鼠中与SARS-CoV-2感染相关的特征与轻度SARS-CoV-2感染的人类相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd1/7394720/6b9833e2c97d/nihms-1592410-f0004.jpg

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