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使用免疫抑制叙利亚仓鼠建立的新大陆汉坦病毒致死性疾病模型。

A lethal disease model for New World hantaviruses using immunosuppressed Syrian hamsters.

作者信息

Vergote Valentijn, Laenen Lies, Vanmechelen Bert, Van Ranst Marc, Verbeken Erik, Hooper Jay W, Maes Piet

机构信息

KU Leuven-University of Leuven, Department of Microbiology and Immunology, Laboratory of Clinical Virology, Zoonotic Infectious Diseases unit, Leuven, Belgium.

KU Leuven-University of Leuven, Department of Imaging & Pathology, Translational Cell and Tissue Research, Leuven, Belgium.

出版信息

PLoS Negl Trop Dis. 2017 Oct 27;11(10):e0006042. doi: 10.1371/journal.pntd.0006042. eCollection 2017 Oct.

Abstract

BACKGROUND

Hantavirus, the hemorrhagic causative agent of two clinical diseases, is found worldwide with variation in severity, incidence and mortality. The most lethal hantaviruses are found on the American continent where the most prevalent viruses like Andes virus and Sin Nombre virus are known to cause hantavirus pulmonary syndrome. New World hantavirus infection of immunocompetent hamsters results in an asymptomatic infection except for Andes virus and Maporal virus; the only hantaviruses causing a lethal disease in immunocompetent Syrian hamsters mimicking hantavirus pulmonary syndrome in humans.

METHODOLOGY/PRINCIPAL FINDINGS: Hamsters, immunosuppressed with dexamethasone and cyclophosphamide, were infected intramuscularly with different New World hantavirus strains (Bayou virus, Black Creek Canal virus, Caño Delgadito virus, Choclo virus, Laguna Negra virus, and Maporal virus). In the present study, we show that immunosuppression of hamsters followed by infection with a New World hantavirus results in an acute disease that precisely mimics both hantavirus disease in humans and Andes virus infection of hamsters.

CONCLUSIONS/ SIGNIFICANCE: Infected hamsters showed specific clinical signs of disease and moreover, histological analysis of lung tissue showed signs of pulmonary edema and inflammation within alveolar septa. In this study, we were able to infect immunosuppressed hamsters with different New World hantaviruses reaching a lethal outcome with signs of disease mimicking human disease.

摘要

背景

汉坦病毒是两种临床疾病的出血病原体,在全球范围内均有发现,其严重程度、发病率和死亡率存在差异。最致命的汉坦病毒存在于美洲大陆,在那里,安第斯病毒和辛诺柏病毒等最常见的病毒已知会导致汉坦病毒肺综合征。除安第斯病毒和马波拉尔病毒外,免疫功能正常的仓鼠感染新大陆汉坦病毒会导致无症状感染;这是仅有的两种能在免疫功能正常的叙利亚仓鼠中引发致命疾病、类似于人类汉坦病毒肺综合征的汉坦病毒。

方法/主要发现:用 dexamethasone 和 cyclophosphamide 进行免疫抑制的仓鼠通过肌肉注射感染不同的新大陆汉坦病毒株(河口病毒、黑溪运河病毒、卡尼奥德尔加迪托病毒、乔克洛病毒、拉古纳内格拉病毒和马波拉尔病毒)。在本研究中,我们表明,对仓鼠进行免疫抑制后再感染新大陆汉坦病毒会导致一种急性疾病,该疾病精确模拟了人类的汉坦病毒病和仓鼠的安第斯病毒感染。

结论/意义:受感染的仓鼠表现出特定的疾病临床症状,此外,肺组织的组织学分析显示肺泡间隔内有肺水肿和炎症迹象。在本研究中,我们能够用不同的新大陆汉坦病毒感染免疫抑制的仓鼠,导致致命结果,并出现类似于人类疾病的症状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b64d/5678717/56608d299a3f/pntd.0006042.g001.jpg

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