Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever
Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever
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DOI：
10.1186/1743-422x-9-122
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发表时间：
2012-06-19
期刊：
影响因子：
4.8
通讯作者：
Bente, Dennis A.
中科院分区：
文献类型：
--
作者：
Bowick, Gavin C.;Airo, Adriana M.;Bente, Dennis A.
研究背景：克里米亚刚果出血热（CCHF）是一种蜱传出血性人兽共患病，病死率高。由于缺乏合适的动物模型，CCHF的发病机制研究以及疫苗和抗病毒药物的开发受到严重阻碍。我们最近开发了一个成熟的小鼠模型CCHF使用携带STAT1基因敲除（KO）的小鼠，其特点是：鉴于干扰素在控制病毒感染的重要性，我们研究了干扰素通路相关基因的表达KO和野生型（WT）小鼠CCHF病毒的挑战。我们预期STAT1蛋白的缺失将导致IFN相关基因的最小表达。令人惊讶的是，KO小鼠在感染后第2天开始显示出高水平的IFN刺激的基因表达，而在用病毒攻击的WT小鼠中，相同的基因在第1天以相似的水平表达。结论：我们得出结论，CCHF病毒在STAT1 KO和WT小鼠中诱导相似的I型IFN应答，但是KO小鼠中的延迟应答允许快速病毒传播和致命疾病。
Background: Crimean Congo hemorrhagic fever (CCHF) is a tick-borne hemorrhagic zoonosis associated with high mortality. Pathogenesis studies and the development of vaccines and antivirals against CCHF have been severely hampered by the lack of suitable animal model. We recently developed and characterized a mature mouse model for CCHF using mice carrying STAT1 knockout (KO).Findings: Given the importance of interferons in controlling viral infections, we investigated the expression of interferon pathway-associated genes in KO and wild-type (WT) mice challenged with CCHF virus. We expected that the absence of the STAT1 protein would result in minimal expression of IFN-related genes. Surprisingly, the KO mice showed high levels of IFN-stimulated gene expression, beginning on day 2 post-infection, while in WT mice challenged with virus the same genes were expressed at similar levels on day 1.Conclusions: We conclude that CCHF virus induces similar type I IFN responses in STAT1 KO and WT mice, but the delayed response in the KO mice permits rapid viral dissemination and fatal illness.