A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever

A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever
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DOI:
10.1086/514292
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发表时间:
1999-02-01
影响因子:
6.4
通讯作者:
Huggins, J
Huggins, J
中科院分区:
医学2区
文献类型:
--
作者:
Bray, M;Davis, K;Huggins, J

文献摘要

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扎伊尔亚型埃博拉病毒(EBO-Z)对新生小鼠是致命的,但成年小鼠对该病毒具有抗性,这阻止了它们用作致死性埃博拉感染的动物模型。我们在逐渐变老的乳鼠中连续传代EBO-Z病毒,最终获得对成熟的免疫活性BALB/c和C57 BL/6近交系和ICR(CD-1)远交系小鼠是致命的噬斑纯化病毒。感染小鼠肝脏和脾脏的病理变化与感染EBO-Z的灵长类动物相似。这些组织中的病毒滴度达到10(9)pfu/g。小鼠适应的EBO-Z病毒接种到腹腔中的LD_(50)近似于1个病毒粒子。小鼠对皮下、皮内或肌内接种的大剂量相同病毒具有抗性。外周注射小鼠适应性EBO-Z病毒或腹膜内注射非适应性EBO-Z病毒的小鼠抵抗随后的小鼠适应性病毒攻击。
The Zaire subtype of Ebola virus (EBO-Z) is lethal for newborn mice, but adult mice are resistant to the virus, which prevents their use as an animal model of lethal Ebola infection, We serially passed EBO-Z virus in progressively older suckling mice, eventually obtaining a plaque-purified virus that was lethal for mature, immunocompetent BALB/c and C57BL/6 inbred and ICR (CD-1) outbred mice. Pathologic changes in the liver and spleen of infected mice resembled those in EBO-Z-infected primates. Virus titers in these tissues reached 10(9) pfu/g, The LD50 of mouse-adapted EBO-Z virus inoculated into the peritoneal cavity was similar to 1 virion. Mice were resistant to large doses of the same virus inoculated subcutaneously, intradermally, or intramuscularly, Mice injected peripherally with mouse-adapted or intraperitoneally with non-adapted EBO-Z virus resisted subsequent challenge with mouse-adapted virus.