Type I interferon underlies severe disease associated with Junin virus infection in mice
Type I interferon underlies severe disease associated with Junin virus infection in mice
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DOI：
10.7554/elife.55352
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发表时间：
2020-05-26
期刊：
影响因子：
7.7
通讯作者：
Gowen, Brian B.
中科院分区：
文献类型：
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作者：
Hickerson, Brady T.;Sefing, Eric J.;Gowen, Brian B.
朱宁病毒（JUNV）是五种新世界哺乳动物肾病毒（NWM）之一，可引起人类致命性出血性疾病，是阿根廷出血热（AHF）的病原体。AHF的发病机制尚不清楚;然而，长期的、升高的干扰素-α（IFN-α）反应与阴性疾病结局相关。引起病毒性出血热的所有NWM的一个特征是使用人转铁蛋白受体1（hTfR 1）进入细胞。在这里，我们表明，表达hTfR 1的小鼠发展一个致命的疾病过程中，血清IFN-α浓度的增加时，与JUNV的挑战。此外，我们提供的证据表明，I型干扰素反应是中央严重JUNV疾病的hTfR 1小鼠的发展。我们的研究结果确定hTfR 1介导的进入和I型IFN反应作为JUNV感染小鼠发病机制的关键因素。
Junin virus (JUNV) is one of five New World mammarenaviruses (NWMs) that causes fatal hemorrhagic disease in humans and is the etiological agent of Argentine hemorrhagic fever (AHF). The pathogenesis underlying AHF is poorly understood; however, a prolonged, elevated interferon-alpha (IFN-alpha) response is associated with a negative disease outcome. A feature of all NWMs that cause viral hemorrhagic fever is the use of human transferrin receptor 1 (hTfR1) for cellular entry. Here, we show that mice expressing hTfR1 develop a lethal disease course marked by an increase in serum IFN-alpha concentration when challenged with JUNV. Further, we provide evidence that the type I IFN response is central to the development of severe JUNV disease in hTfR1 mice. Our findings identify hTfR1-mediated entry and the type I IFN response as key factors in the pathogenesis of JUNV infection in mice.