State Key Laboratory of Virology, School of Health Sciences, Wuhan University, Wuhan, China.
Institute of Pathogenic Microbiology, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, China.
Front Immunol. 2021 Feb 23;12:595140. doi: 10.3389/fimmu.2021.595140. eCollection 2021.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus that causes hemorrhagic fever. Previous studies showed that SFTSV-infected patients exhibited elevated levels of pro-inflammatory cytokines like interleukin-1β (IL-1β), indicating that SFTSV infection may activate inflammasomes. However, the detailed mechanism remains poorly understood. Herein, we found that SFTSV could stimulate the IL-1β secretion in the infected human peripheral blood mononuclear cells (PBMCs), human macrophages, and C57/BL6 mice. We demonstrate that the maturation and secretion of IL-1β during SFTSV infection is mediated by the nucleotide and oligomerization domain, leucine-rich repeat-containing protein family, pyrin-containing domain 3 (NLRP3) inflammasome. This process is dependent on protease caspase-1, a component of the NLRP3 inflammasome complex. For the first time, our study discovered the role of NLRP3 in response to SFTSV infection. This finding may lead to the development of novel drugs to impede the pathogenesis of SFTSV infection.
严重发热伴血小板减少综合征病毒（SFTSV）是一种新兴的蜱传病毒，可引起出血热。先前的研究表明，SFTSV 感染患者表现出促炎细胞因子（如白细胞介素 1β（IL-1β））水平升高，表明 SFTSV 感染可能激活炎症小体。然而，其详细机制尚不清楚。在此，我们发现 SFTSV 可刺激感染的人外周血单核细胞（PBMCs）、人巨噬细胞和 C57/BL6 小鼠中 IL-1β 的分泌。我们证明，SFTSV 感染期间 IL-1β 的成熟和分泌是由核苷酸和寡聚域、富含亮氨酸重复序列的蛋白家族、含 pyrin 结构域 3（NLRP3）炎症小体介导的。该过程依赖于蛋白酶半胱天冬酶-1，这是 NLRP3 炎症小体复合物的组成部分。本研究首次发现 NLRP3 在应对 SFTSV 感染中的作用。这一发现可能为开发新型药物以抑制 SFTSV 感染的发病机制提供依据。
