Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections

伴有血小板减少症的严重发热综合征病毒在致命的人类感染中靶向B细胞

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作者:Tadaki Suzuki ,Yuko Sato ,Kaori Sano ,Takeshi Arashiro ,Harutaka Katano ,Noriko Nakajima ,Masayuki Shimojima ,Michiyo Kataoka ,Kenta Takahashi ,Yuji Wada ,Shigeru Morikawa ,Shuetsu Fukushi ,Tomoki Yoshikawa ,Masayuki Saijo ,Hideki Hasegawa

Abstract

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.

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