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Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections
Tadaki Suzuki, … , Masayuki Saijo, Hideki Hasegawa
Tadaki Suzuki, … , Masayuki Saijo, Hideki Hasegawa
Published January 6, 2020
Citation Information: J Clin Invest. 2020;130(2):799-812. https://doi.org/10.1172/JCI129171.
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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 5

Peripheral-blood plasmablasts do not show higher susceptibility to SFTSV infection among peripheral-blood B cells in healthy adults.

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Peripheral-blood plasmablasts do not show higher susceptibility to SFTSV...
(A) Flow cytometry gating strategy to define lymphocyte subsets by CD3, CD19, CD27, and CD38 in SFTSV-inoculated PBMCs obtained from healthy donors (n = 11). The infectivity of SFTSV in each subset was determined by intracellular staining with DyLight 488–conjugated anti–SFTSV N antibody at 24 hours after inoculation. (B) Comparison of SFTSV infectivity among CD19− (blue), CD19+ (red), or CD3+ (green) lymphocytes in SFTSV-inoculated PBMCs. CD19+ B cells showed higher susceptibility to SFTSV than CD3+ T cells or CD19− non-B cells. Scatter plots also show mean ± SD. ****P < 0.0001 (1-way ANOVA followed by Holm-Sidak’s multiple-comparisons test). (C) Comparison of SFTSV infectivity between CD19+ B cells (red) and CD3−CD19+CD27+CD38+ plasmablasts (PB, purple). The SFTSV-infected cells in CD19+ B cells were not biased to the PB fraction. Scatter plots also show paired lines (n = 11). **P = 0.0024 (paired t test).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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