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裂谷热病毒气溶胶感染基因敲除仓鼠的发病机制。

Pathogenesis of Rift Valley Fever Virus Aerosol Infection in Knockout Hamsters.

机构信息

Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA.

Utah Veterinary Diagnostic Laboratory, Logan, UT 84341, USA.

出版信息

Viruses. 2018 Nov 19;10(11):651. doi: 10.3390/v10110651.

DOI:10.3390/v10110651
PMID:30463176
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6265887/
Abstract

Rift Valley fever virus (RVFV) is an emerging pathogen capable of causing severe disease in livestock and humans and can be transmitted by multiple routes including aerosol exposure. Several animal models have been developed to gain insight into the pathogenesis associated with aerosolized RVFV infection, but work with these models is restricted to high containment biosafety level (BSL) laboratories limiting their use for antiviral and vaccine development studies. Here, we report on a new RVFV inhalation infection model in KO hamsters exposed to aerosolized MP-12 vaccine virus by nose-only inhalation that enables a more accurate delivery and measurement of exposure dose. RVFV was detected in hepatic and other tissues 4⁻5 days after challenge, consistent with virus-induced lesions in the liver, spleen and lung. Furthermore, assessment of blood chemistry and hematological parameters revealed alterations in several liver disease markers and white blood cell parameters. Our results indicate that KO hamsters develop a disease course that shares features of disease observed in human cases and in other animal models of RVFV aerosol exposure, supporting the use of this BSL-2 infection model for countermeasure development efforts.

摘要

裂谷热病毒(RVFV)是一种新兴的病原体,能够在牲畜和人类中引起严重疾病,并且可以通过多种途径传播,包括气溶胶暴露。已经开发了几种动物模型来深入了解与气溶胶化 RVFV 感染相关的发病机制,但这些模型的工作仅限于高生物安全级别(BSL)实验室,限制了它们在抗病毒和疫苗开发研究中的使用。在这里,我们报告了一种新的裂谷热病毒吸入感染模型,KO 仓鼠通过鼻吸入仅暴露于气溶胶化的 MP-12 疫苗病毒,这使得更准确地传递和测量暴露剂量成为可能。在挑战后 4-5 天,在肝和其他组织中检测到 RVFV,与肝、脾和肺中的病毒诱导损伤一致。此外,对血液化学和血液学参数的评估显示,几种肝病标志物和白细胞参数发生了改变。我们的结果表明,KO 仓鼠发展出一种疾病过程,其具有与人类病例和其他 RVFV 气溶胶暴露动物模型中观察到的疾病特征相似,支持使用这种 BSL-2 感染模型进行对策开发工作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ff/6265887/a85956fdc790/viruses-10-00651-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ff/6265887/f53bf3fbd89f/viruses-10-00651-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ff/6265887/b3638c2f733b/viruses-10-00651-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ff/6265887/1c4e5064f24e/viruses-10-00651-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ff/6265887/fcea6b83871d/viruses-10-00651-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ff/6265887/a85956fdc790/viruses-10-00651-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ff/6265887/f53bf3fbd89f/viruses-10-00651-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ff/6265887/b3638c2f733b/viruses-10-00651-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ff/6265887/1c4e5064f24e/viruses-10-00651-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ff/6265887/fcea6b83871d/viruses-10-00651-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9ff/6265887/a85956fdc790/viruses-10-00651-g005.jpg

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本文引用的文献

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Rift Valley Fever.裂谷热
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病毒降解细胞信号转导和转录激活因子 2 的机制。
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