Department of Critical Care Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Centers for Disease Control and Prevention, Hangzhou, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China.
School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China.
J Thromb Haemost. 2023 May;21(5):1336-1351. doi: 10.1016/j.jtha.2023.02.006. Epub 2023 Feb 13.
Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) infection causes an emerging hemorrhagic fever in East Asia with a high mortality rate. Thrombocytopenia is a consistent feature of SFTS illness, but the mechanism remains elusive.
We aimed to better understand the role of platelets in the pathophysiology of SFTSV infection, including the development of thrombocytopenia.
Using platelets from healthy volunteers and patients with SFTS, we evaluated the functional changes in platelets against SFTSV infection. We investigated the direct effect of glycoprotein VI on platelet-SFTSV interaction by quantitative real-time PCR, molecular docking, surface plasmon resonance spectrometry, flow cytometry, western blot, and platelet functional studies in vitro. Interactions of SFTSV and platelet-SFTSV complexes with macrophages were also determined by scanning electron microscope, quantitative real-time PCR, and flow cytometry.
This study is the first to demonstrate that platelets are capable of harboring and producing SFTSV particles. Structural and functional studies found that SFTSVs bind platelet glycoprotein VI to potentiate platelet activation, including platelet aggregation, adenosine triphosphate release, spreading, clot retraction, coagulation, phosphatidylserine exposure, thrombus formation, and adherence. In vitro mechanistic studies highlighted that the interaction of platelets with human THP-1 cells promoted SFTSV clearance and suppressed cytokine production in macrophages. However, unwanted SFTSV replication in macrophages reciprocally aggravated SFTSV persistence in the circulation, which may contribute to thrombocytopenia and other complications during SFTSV infection.
These findings together highlighted the pathophysiological role of platelets in initial intrinsic defense against SFTSV infections, as well as intertwined processes with host immunity, which can also lead to thrombocytopenia and poor prognosis.
严重发热伴血小板减少综合征病毒（SFTSV）感染引起的一种新发出血热，在东亚地区死亡率较高。血小板减少是 SFTS 疾病的一个特征，但发病机制尚不清楚。
我们旨在更好地了解血小板在 SFTSV 感染发病机制中的作用，包括血小板减少症的发生机制。
使用来自健康志愿者和 SFTS 患者的血小板，我们评估了血小板对 SFTSV 感染的功能变化。我们通过实时定量 PCR、分子对接、表面等离子体共振光谱法、流式细胞术、western blot 和体外血小板功能研究，研究了糖蛋白 VI 对血小板-SFTSV 相互作用的直接影响。还通过扫描电子显微镜、实时定量 PCR 和流式细胞术确定了 SFTSV 和血小板-SFTSV 复合物与巨噬细胞的相互作用。
这项研究首次表明血小板能够携带和产生 SFTSV 颗粒。结构和功能研究发现，SFTSVs 结合血小板糖蛋白 VI 以增强血小板激活，包括血小板聚集、三磷酸腺苷释放、铺展、凝块回缩、凝血、血小板膜磷脂酰丝氨酸暴露、血栓形成和黏附。体外机制研究强调了血小板与人类 THP-1 细胞的相互作用促进了 SFTSV 的清除，并抑制了巨噬细胞中的细胞因子产生。然而，巨噬细胞中不受控制的 SFTSV 复制反过来加重了 SFTSV 在循环中的持续存在，这可能导致 SFTSV 感染期间血小板减少症和其他并发症。
这些发现共同强调了血小板在 SFTSV 感染初始固有防御中的病理生理学作用，以及与宿主免疫的交织过程，这也可能导致血小板减少症和预后不良。
