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用于克里米亚-刚果出血热病毒的免疫功能正常的小鼠模型。

Immunocompetent mouse model for Crimean-Congo hemorrhagic fever virus.

机构信息

Laboratory of Virology, Division of Intramural Research, NIAID, NIH, Hamilton, United States.

Texas Veterinary Pathology, Spring Branch, United States.

出版信息

Elife. 2021 Jan 8;10:e63906. doi: 10.7554/eLife.63906.

DOI:10.7554/eLife.63906
PMID:33416494
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7811403/
Abstract

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. CCHF is caused by infection with the Crimean-Congo hemorrhagic fever virus (CCHFV) and case fatality rates can be as high as 30%. Despite causing severe disease in humans, our understanding of the host and viral determinants of CCHFV pathogenesis are limited. A major limitation in the investigation of CCHF has been the lack of suitable small animal models. Wild-type mice are resistant to clinical isolates of CCHFV and consequently, mice must be deficient in type I interferon responses to study the more severe aspects of CCHFV. We report here a mouse-adapted variant of CCHFV that recapitulates in adult, immunocompetent mice the severe CCHF observed in humans. This mouse-adapted variant of CCHFV significantly improves our ability to study host and viral determinants of CCHFV-induced disease in a highly tractable mouse model.

摘要

克里米亚-刚果出血热（CCHF）是一种严重的蜱传发热疾病，具有广泛的地理分布。CCHF 是由克里米亚-刚果出血热病毒（CCHFV）感染引起的，病死率可高达 30%。尽管 CCHFV 在人类中引起严重疾病，但我们对宿主和病毒决定因素的了解有限。CCHF 研究的一个主要限制是缺乏合适的小动物模型。野生型小鼠对 CCHFV 的临床分离株具有抗性，因此，必须缺乏 I 型干扰素反应才能研究 CCHFV 更严重的方面。我们在这里报告了一种适应小鼠的 CCHFV 变体，该变体在成年免疫功能正常的小鼠中重现了人类中观察到的严重 CCHF。这种适应小鼠的 CCHFV 变体显著提高了我们在高度可处理的小鼠模型中研究宿主和病毒决定因素引起的 CCHFV 疾病的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b8/7811403/63a18fb5f79d/elife-63906-resp-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b8/7811403/4478edf7d4ab/elife-63906-fig1-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b8/7811403/1865d9198f0f/elife-63906-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b8/7811403/d444c7ac9394/elife-63906-fig3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b8/7811403/d91f8cd0142a/elife-63906-fig5.jpg
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