Abstract
BACKGROUND: Thrombocytopenia is the major clinical feature of severe fever with thrombocytopenia syndrome (SFTS), but the mechanism by which it occurs remains unclear. METHODS: RNA transcriptome analyses were performed on platelets purified from patients with SFTS and mice infected with SFTS virus (SFTSV). The functions of differentially expressed genes (DEGs) in the platelets were characterized. Enzyme-linked immunosorbent assay, flow cytometry, and quantitative reverse-transcription polymerase chain reaction were used to measure the levels of platelet activation, SFTSV infection in platelets, formation of neutrophil extracellular traps, transcription of DEGs, and the percentage of platelets undergoing cell death. RESULTS: Enhanced neutrophil activation and interferon signaling involved in the viral life cycle were common platelet responses in SFTS, which may consume increasing numbers of platelets. Other functional changes may be associated with different outcomes of SFTS. SFTSV infection led to platelet destruction by pyroptosis, apoptosis, necroptosis, and autophagy. Platelets in SFTSV-infected mice mainly play a role in adaptive immunity, and platelet death was not as severe as in humans. CONCLUSIONS: The altered functions of platelets, including mediating leukocyte activation and undergoing cell death, contribute to thrombocytopenia in patients with SFTS. The different mechanisms of thrombocytopenia in mice suggest that platelet functions should be considered in experimental animal models.