Rescue of a Recombinant Machupo Virus from Cloned cDNAs and In Vivo Characterization in Interferon (αβ/γ) Receptor Double Knockout Mice

Rescue of a Recombinant Machupo Virus from Cloned cDNAs and In Vivo Characterization in Interferon (αβ/γ) Receptor Double Knockout Mice
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DOI:
10.1128/jvi.02925-13
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发表时间:
2014-02-01
影响因子:
5.4
通讯作者:
Paessler, Slobodan
Paessler, Slobodan
中科院分区:
医学2区
文献类型:
--
作者:
Patterson, Michael;Seregin, Alexey;Paessler, Slobodan

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马丘波病毒(MACV)是玻利维亚出血热(BHF)的病原体,BHF是一种重新出现和被忽视的热带疾病,与高死亡率相关。MACV的原型毒株Carvallo于1963年从一名人类患者中分离出来,但已报道了最少的体外和体内表征。为此,我们利用反向遗传学从克隆的cDNA中拯救致病性MACV。重组MACV(rMACV)的体外生长特性与亲本MACV相似。两种病毒在α/β和γ干扰素受体敲除小鼠中引起相似的疾病发展,包括神经系统疾病发展和高死亡率。此外,我们已经确定了一种新的小鼠模型,其死亡率和神经系统疾病与人类和非人灵长类动物中报告的BHF疾病相似。
Machupo virus (MACV) is the etiological agent of Bolivian hemorrhagic fever (BHF), a reemerging and neglected tropical disease associated with high mortality. The prototypical strain of MACV, Carvallo, was isolated from a human patient in 1963, but minimal in vitro and in vivo characterization has been reported. To this end, we utilized reverse genetics to rescue a pathogenic MACV from cloned cDNAs. The recombinant MACV (rMACV) had in vitro growth properties similar to those of the parental MACV. Both viruses caused similar disease development in alpha/beta and gamma interferon receptor knockout mice, including neurological disease development and high mortality. In addition, we have identified a novel murine model with mortality and neurological disease similar to BHF disease reported in humans and nonhuman primates.