Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections
Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections
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DOI：
10.1172/jci129171
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发表时间：
2020-02-03
影响因子：
15.9
通讯作者：
Hasegawa, Hideki
中科院分区：
文献类型：
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作者：
Suzuki, Tadaki;Sato, Yuko;Hasegawa, Hideki
严重发热伴血小板减少综合征(SFTS)是一种由壁虱传播的悦阳病毒引起的新发出血热，与高病死率有关。尽管在东亚地区SFTS的发病率不断上升，并引起了严重的公共卫生问题，但人类致死性SFTS病毒(SFTSV)感染的发病机制尚不完全清楚。到目前为止，确定病毒感染目标细胞的尸检数量有限。结果表明，在致死性感染末期，次级淋巴器官中分化为浆母细胞和巨噬细胞的B细胞是SFTSV的靶细胞，感染的细胞大多为B细胞系淋巴细胞。在感染SFTSV的患者中，B细胞系淋巴细胞广泛分布于淋巴和非淋巴器官中，偶尔可见这些细胞向器官的毛细血管内渗透。此外，人浆母细胞淋巴瘤细胞系PBL-1对SFTSV增殖敏感，其免疫表型与SFTSV在致死性SFTS中的靶细胞相似。因此，PBL-1可以提供一种潜在的人SFTSV感染的体外模型。这些结果加深了我们对人类致死性SFTSV感染发病机制的理解，并有助于制定SFTSV对策。
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne banyangvirus and is associated with high fatality. Despite increasing incidence of SFTS and serious public health concerns in East Asia, the pathogenesis of lethal SFTS virus (SFTSV) infection in humans is not fully understood. Numbers of postmortem examinations to determine target cells of the viral infection have so far been limited. Here we showed that B cells differentiating into plasmablasts and macrophages in secondary lymphoid organs were targets for SFTSV at the end stage of lethal infection, and the majority of SFTSV-infected cells were B cell-lineage lymphocytes. In affected individuals, B cell-lineage lymphocytes with SFTSV infection were widely distributed in both lymphoid and nonlymphoid organs, and infiltration of these cells into the capillaries of the organs could be observed occasionally. Moreover, a human plasmablastic lymphoma cell line, PBL-1, was susceptible to SFTSV propagation and had a similar immunophenotype to that of target cells of SFTSV in fatal SFTS. PBL-1 can therefore provide a potential in vitro model for human SFTSV infection. These results extend our understanding of the pathogenesis of human lethal SFTSV infection and can facilitate the development of SFTSV countermeasures.