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Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections
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
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
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Research Article Infectious disease Virology

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

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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.

Authors

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

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Figure 3

SFTSV-infected B cells infiltrate nonlymphoid organs in fatal SFTS.

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SFTSV-infected B cells infiltrate nonlymphoid organs in fatal SFTS.
(A) ...
(A) Representative pathological images of the liver, adrenal gland, intestine, lung, heart, and tissue capillary (renal medulla) in individuals who died from SFTS. H&E staining (upper panels) or IHC for SFTSV N protein (lower panels). Pie charts show the number of individuals whose tissues were analyzed, and the percentage in whose tissues SFTSV antigen was detected by IHC. Scale bars: 100 μm or 20 μm (capillary). (B) SFTSV IHC scores for tissue sections of lymph nodes (LNs; n = 20), and nonlymphoid organs: liver (n = 21), adrenal gland (n = 13), intestine (n = 14), lung (n = 17), kidney (n = 16), and heart (n = 11). IHC scores for nonlymphoid organs were significantly lower than for LNs. Scatter plots also show mean ± SD. The P values were calculated with 1-way ANOVA followed by Holm-Sidak’s multiple-comparisons test to make comparisons between the IHC scores of nonlymphoid organs and those of LNs. (C) IHC for SFTSV N, B cell (CD20 and MUM1), and macrophage (CD163) markers in serial tissue sections of nonlymphoid organs from individuals who died from SFTS. Regions with SFTSV+ cells had B cell infiltration. Scale bars: 50 μm.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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