Animal Models of Emerging Tick-Borne Phleboviruses: Determining Target Cells in a Lethal Model of SFTSV Infection.
Animal Models of Emerging Tick-Borne Phleboviruses: Determining Target Cells in a Lethal Model of SFTSV Infection.
复制标题
新兴tick传播静脉病毒的动物模型：在SFTSV感染的致命模型中确定靶细胞。
DOI：
10.3389/fmicb.2017.00104
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发表时间：
2017
影响因子：
5.2
通讯作者：
Ebihara H
中科院分区：
文献类型：
--
作者：
Matsuno K;Orba Y;Maede-White K;Scott D;Feldmann F;Liang M;Ebihara H
新出现的蜱传静脉病毒引起的临床表现的发病机制[即，严重发热伴血小板减少综合征病毒（SFTSV）和Heartland病毒（HRTV）]，如严重血小板减少症和淋巴细胞减少症，尚未完全了解。在本研究中，为了建立一种模仿致命人类病例特征的动物模型，我们检查了来自12个品系的成年小鼠、来自两个品系的老年小鼠和食蟹猴对SFTSV和/或HRTV感染的易感性。然而，这些免疫活性动物感染SFTSV或HRTV后均未发生致死性疾病。因此，我们使用干扰素-α/β受体敲除（IFNAR-/-）小鼠测试了SFTSV感染的致死动物模型，以鉴定病毒感染的靶细胞以及可能与血液学变化相关的病变。在IFNAR-/-小鼠的脾和淋巴结中，IbaI阳性巨噬细胞和Pax 5阳性未成熟B细胞与SFTSV阳性细胞重叠，在肝脏和肾脏中也观察到IbaI-SFTSV双阳性细胞，从而表明巨噬细胞在SFTSV感染小鼠的发病机制中起关键作用。在感染小鼠的下颌淋巴结和脾脏中，我们观察到包括B220阳性B细胞的广泛坏死，这可能与严重的淋巴细胞减少症有关。这项研究的结果表明，IFNAR-/-小鼠模型和人类致死性感染之间的相似性，以及多种细胞在小鼠发病过程中的作用。
The pathogenesis of clinical manifestations caused by newly emerging tick-borne phleboviruses [i.e., Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV)], such as severe thrombocytopenia and lymphocytopenia, are not yet fully understood. In the present study, to establish an animal model mimicking the profile of fatal human cases, we examined the susceptibilities of adult mice from 12 strains, aged mice from two strains, and cynomolgus macaques to SFTSV and/or HRTV infections. However, none of these immunocompetent animals developed lethal diseases after infection with SFTSV or HRTV. Thus, we tested a lethal animal model of SFTSV infection using interferon-α/β receptor knock-out (IFNAR-/-) mice to identify the target cell(s) of virus infection, as well as lesions that are potentially associated with hematological changes. IbaI-positive macrophages and Pax5-positive immature B cells overlapped with SFTSV-positive cells in the spleen and lymph nodes of IFNAR-/- mice, and IbaI-SFTSV-double positive cells were also observed in the liver and kidney, thereby suggesting crucial roles for macrophages in the pathogenesis of SFTSV infection in mice. In the mandibular lymph nodes and spleens of infected mice, we observed extensive necrosis comprising B220-positive B cells, which may be associated with severe lymphocytopenia. The results of this study suggest a resemblance between the IFNAR-/- mouse model and lethal infections in humans, as well as roles for multiple cells during pathogenesis in mice.