Depletion but Activation of CD56dimCD16+ NK Cells in Acute Infection with Severe Fever with Thrombocytopenia Syndrome Virus

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality (12%–30%). The mechanism by which the SFTS bunyavirus (SFTSV) causes severe illness remains unclear. To evaluate the phenotypic and functional characteristics of the NK cell subsets in SFTS patients, twenty-nine SFTS patients were sequentially sampled from admission until recovery. Phenotypic and functional characteristics of NK cell subsets in circulating blood were analysed via flow cytometry. Then, correlations between NK cell subset frequencies and the SFTS index (SFTSI) were evaluated in all SFTS patients (15 mild, 14 severe) upon admission. The frequencies of CD56dimCD16+ NK cells were greatly decreased in early SFTSV infection and were negatively correlated with disease severity. Additionally, higher Ki-67 and granzyme B expression and relatively lower NKG2A expression in CD56dimCD16+ NK cells were observed in acute infection. Moreover, the effector function of CD56dim NK cells was increased in the acute phase compared with the recovery phase in nine severe SFTS patients. Additionally, interleukin (IL)-15, interferon (IFN)-α, IL-18 and IFN-γ secretion was markedly increased during early infection. Collectively, despite depletion of CD56dimCD16+ NK cells, activation and functional enhancement of CD56dimCD16+ NK cells were still observed, suggesting their involvement in defence against early SFTSV infection.

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Acknowledgements

We thank all of the donors and patients for participating in this research. This study was supported by the National Natural Science Foundation of China (81271884) and of Hubei (2018CFB471). The funding source played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Contributions

ML, YX, CP and XZ conceived and designed the experiments. ML, YX, MYL and WZ performed the experiments. ML and YX analyzed the data. ML and YX wrote the manuscript and prepared the Figures. YZ, SX, CZ and BL provided resources. JL, ML, and DY provided helpful suggestion about the study. CP and XZ checked and finalized the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Cheng Peng or Xin Zheng.

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The authors declare that they have no conflicts of interest.

Animal and Human Rights Statement

The research protocol was approved by the Ethics Committee of Tongji Medical College of Huazhong University of Science and Technology. Written informed consent was obtained from all participants prior to blood collection.

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Li, M., Xiong, Y., Li, M. et al. Depletion but Activation of CD56dimCD16+ NK Cells in Acute Infection with Severe Fever with Thrombocytopenia Syndrome Virus. Virol. Sin. 35, 588–598 (2020). https://doi.org/10.1007/s12250-020-00224-3

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Keywords

  • Severe fever with thrombocytopenia syndrome Virus (SFTSV)
  • SFTS index
  • NK cell subsets
  • Phenotypic of CD56dimCD16+ NK cells
  • Function of CD56dimCD16+ NK cells