Host genetic variation in susceptibility to Punta Toro virus.

Host genetic variation in susceptibility to Punta Toro virus.
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DOI:
10.1016/j.virusres.2011.02.008
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发表时间:
2011-04
期刊:
影响因子:
5
通讯作者:
Spindler KR
Spindler KR
中科院分区:
医学3区
文献类型:
--
作者:
Ashley SL;Ameres SM;Gerrard SR;Foreman O;Eaton KA;Weinberg JB;Spindler KR

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蓬塔托罗病毒(PTV)是布尼亚病毒科、白蛉病毒属的一种小型实验动物感染病毒,是研究人类病原裂谷热病毒(RVFV)的模型。我们已经确定了近交系小鼠品系的显着差异,在主机响应的Adames株的PTV。在存活实验中,用高剂量PTV皮下接种代表小家鼠中主要分支的9个近交系小鼠。两个近交系小鼠,NZW/LacJ和129 S1/SvImJ,在PTV感染后约4天死亡,而其他7个品系在攻击中存活,没有显示出疾病的临床体征。在组织学上,129 S1/SvImJ小鼠表现出大面积肝细胞坏死,并且在肺、脑和脾中具有额外的病变,而NZW/LacJ小鼠具有轻度的碎片状肝细胞坏死。用逆转录酶定量PCR法检测PTV感染小鼠肝脏中病毒载量。表现出临床症状并死于PTV感染的品系的近交小鼠的肝脏病毒载量高于耐药品系的小鼠。通过将易感的129 S1和抗性FVB/N小鼠杂交产生杂交F1小鼠,并测试其易感性。杂交F1小鼠肝脏中的病毒载量显著高于耐药亲本FVB/N小鼠,表明易感性占主导地位。这些发现将使一个公正的遗传方法,以确定宿主基因介导的易感性PTV。
Infection of small laboratory animals by Punta Toro virus (PTV), family Bunyaviridae, genus Phlebovirus, is a model for the study of the human pathogen Rift Valley fever virus (RVFV). We have identified inbred mouse strains with significant differences in host response to the Adames strain of PTV. Nine inbred strains of mice representing major branches in the Mus musculus phylogeny were inoculated subcutaneously with a high dose of PTV in survival experiments. Two inbred strains of mice, NZW/LacJ and 129S1/SvImJ, died ~4 days after PTV infection, whereas 7 other strains survived the challenge and showed no clinical signs of disease. Histologically, 129S1/SvImJ mice showed massive hepatocellular necrosis and had additional lesions in lung, brain, and spleen, whereas NZW/LacJ mice had mild piecemeal hepatocellular necrosis. PTV viral loads in the livers of infected mice were determined by reverse transcriptase quantitative PCR. Inbred mice from strains that showed clinical signs and succumbed to PTV infection had higher liver viral loads than did mice of resistant strains. Hybrid F1 mice were generated by crossing susceptible 129S1 and resistant FVB/N mice and tested for susceptibility. The hybrid F1 mice showed significantly higher viral loads in the liver than the resistant parental FVB/N mice, suggesting that susceptibility is dominant. These findings will enable an unbiased genetic approach to identify host genes mediating susceptibility to PTV.
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发表时间: 2010-03-15
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
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