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王颂基, 曹文广, 何世华, 张子睿, 朱文俊, Estella Moffat, Hideki Ebihara, Carissa Embury-Hyatt, 邱香果. 2018: 马尔堡病毒豚鼠模型的建立及其特征研究. 动物学研究, 39(1): 32-41. DOI: 10.24272/j.issn.2095-8137.2017.054
引用本文: 王颂基, 曹文广, 何世华, 张子睿, 朱文俊, Estella Moffat, Hideki Ebihara, Carissa Embury-Hyatt, 邱香果. 2018: 马尔堡病毒豚鼠模型的建立及其特征研究. 动物学研究, 39(1): 32-41. DOI: 10.24272/j.issn.2095-8137.2017.054
Gary Wong, Wen-Guang Cao, Shi-Hua He, Zi-Rui Zhang, Wen-Jun Zhu, Estella Moffat, Hideki Ebihara, Carissa Embury-Hyatt, Xiang-Guo Qiu. 2018: Development and characterization of a guinea pig model for Marburg virus. Zoological Research, 39(1): 32-41. DOI: 10.24272/j.issn.2095-8137.2017.054
Citation: Gary Wong, Wen-Guang Cao, Shi-Hua He, Zi-Rui Zhang, Wen-Jun Zhu, Estella Moffat, Hideki Ebihara, Carissa Embury-Hyatt, Xiang-Guo Qiu. 2018: Development and characterization of a guinea pig model for Marburg virus. Zoological Research, 39(1): 32-41. DOI: 10.24272/j.issn.2095-8137.2017.054

马尔堡病毒豚鼠模型的建立及其特征研究

Development and characterization of a guinea pig model for Marburg virus

  • 摘要: 马尔堡病毒的安哥拉毒株(MARV/Ang)可引起人类致命性疾病,死亡率高达90%,但免疫健全的啮齿类动物感染后不会产生任何可观察到的症状。我们的前期工作已建立了马尔堡病毒安哥拉变异株(MARV/Ang-MA)的小鼠模型并对其特征进行了研究,以用于筛选有前景的预防和治疗候选药物。但是在使用作为黄金标准的非人类灵长类动物模型进行测试之前,需要用一种中间动物模型来确认小鼠中的研究结果。在本项研究中,我们用马尔堡病毒的安哥拉临床分离株(MARV/Ang)在豚鼠的肝脏和脾脏中进行了连续的传代,获得了能导致豚鼠100%死亡的变异毒株(MARV/Ang-GA)。感染此毒株的动物会出现线状病毒感染的症状,包括淋巴细胞减少,血小板减少症和导致病毒在肝脏、脾脏、肺和肾脏等主要器官扩散的高病毒血症。豚鼠在感染MARV/Ang-GA 7-9天后死亡,半数致死量(median lethal dose, LD50)计算为1.1×10-1半数组织培养感染剂量(median tissue culture infective dose, TCID50)。MARV/Ang-GA的突变已被检出,并与已知的啮齿动物的MARV/Ang变异序列进行了比较,这可能对未来鉴定MARV/Ang病毒基因组中重要的宿主适应位点的研究提供帮助。

     

    Abstract: The Angolan strain of Marburg virus (MARV/Ang) can cause lethal disease in humans with a case fatality rate of up to 90%, but infection of immunocompetent rodents do not result in any observable symptoms. Our previous work includes the development and characterization of a MARV/Ang variant that can cause lethal disease in mice (MARV/Ang-MA), with the aim of using this tool to screen for promising prophylactic and therapeutic candidates. An intermediate animal model is needed to confirm any findings from mice studies before testing in the gold-standard non-human primate (NHP) model. In this study, we serially passaged the clinical isolate of MARV/Ang in the livers and spleens of guinea pigs until a variant emerged that causes 100% lethality in guinea pigs (MARV/Ang-GA). Animals infected with MARV/Ang-GA showed signs of filovirus infection including lymphocytopenia, thrombocytopenia, and high viremia leading to spread to major organs, including the liver, spleen, lungs, and kidneys. The MARV/Ang-GA guinea pigs died between 7–9 days after infection, and the LD50 was calculated to be 1.1×10–1 TCID50 (median tissue culture infective dose). Mutations in MARV/Ang-GA were identified and compared to sequences of known rodent-adapted MARV/Ang variants, which may benefit future studies characterizing important host adaptation sites in the MARV/Ang viral genome.

     

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