SFTSV exploits PPM1K to inhibit apoptosis through the Bcl-2/BAX/Caspase-3 axis for efficient replication

Qianruo Wang; Baoyan Wang; Penghui Liu; Yuanyuan Li

doi:10.1016/j.virs.2026.09.010

October 2026

. doi: 10.1016/j.virs.2026.09.010

Citation: Qianruo Wang, Baoyan Wang, Penghui Liu, Yuanyuan Li. SFTSV exploits PPM1K to inhibit apoptosis through the Bcl-2/BAX/Caspase-3 axis for efficient replication .VIROLOGICA SINICA, 2026, 41(5) : 1132-1144. http://dx.doi.org/10.1016/j.virs.2026.09.010

SFTSV利用PPM1K通过Bcl-2/BAX/Caspase-3轴抑制细胞凋亡从而实现高效复制

王骞若 ^a,b ,
王宝岩 ^a ,
刘鹏辉 ^a ,
李媛媛 ^a,,

a. 吉林大学动物医学学院, 人兽共患病研究所, 教育部人兽共患病研究重点实验室, 人畜共患传染病重症诊治全国重点实验室;
b. 中国农业科学院哈尔滨兽医研究所, 动物疫病防控全国重点实验室

通讯作者： 李媛媛, li_yuanyuan@jlu.edu.cn
收稿日期： 2026-06-10
录用日期： 2026-09-20

摘要

发热伴血小板减少综合征病毒（SFTSV）可引起发热性疾病，且病死率高，对公共卫生构成日益严重的威胁。然而，SFTSV如何调控宿主细胞存活以促进自身复制的分子机制仍不清楚。本研究通过转录组分析发现，SFTSV感染THP-1细胞显著上调PPM1K的mRNA水平。进一步研究表明，SFTSV感染促进内质网-线粒体接触，并使定位在内质网上的病毒蛋白Gc与定位于线粒体的PPM1K发生相互作用，从而在转录水平和蛋白水平上增强PPM1K表达。在机制上，PPM1K通过Ser248位点促进Bcl-2 Ser70位点去磷酸化，降低Bcl-2泛素化水平并增强其稳定性，从而抑制BAX-Caspase-3信号级联反应，阻断感染细胞的凋亡进程，促进SFTSV复制。综上，本研究揭示了一种此前未被报道的SFTSV宿主劫持机制，即病毒通过Gc–PPM1K轴重塑线粒体相关抗凋亡信号，稳定Bcl-2并抑制细胞凋亡，从而为病毒复制创造有利的细胞环境。
- 发热伴血小板减少综合征病毒（SFTSV）
- , 细胞凋亡
- , 蛋白磷酸酶Mg²⁺/Mn²⁺依赖性1K（PPM1K）
- , BAX–Caspase-3通路

SFTSV exploits PPM1K to inhibit apoptosis through the Bcl-2/BAX/Caspase-3 axis for efficient replication

a. State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China;
b. State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150000, China

Corresponding author: Yuanyuan Li, li_yuanyuan@jlu.edu.cn
Received Date: 10 June 2026
Accepted Date: 20 September 2026

Abstract

SFTSV (Severe fever with thrombocytopenia syndrome virus) causes severe febrile illness with high case fatality rates and poses a growing public health threat, while the molecular basis by which it subverts host survival pathways remains poorly understood. In this study, transcriptomic profiling identified PPM1K as a prominently induced host factor in SFTSV-infected THP-1-derived macrophages. We further demonstrate that SFTSV infection promotes endoplasmic reticulum-mitochondria coupling, enabling the viral glycoprotein Gc to interact with mitochondrial PPM1K and enhance its expression at both transcriptional and protein levels. Mechanistically, the S248 residue of PPM1K is required for its dephosphorylation of Bcl-2, thereby decreasing Bcl-2 ubiquitination and stabilizing its anti-apoptotic activity, which ultimately suppresses the BAX-caspase-3 signaling cascade. This anti-apoptotic remodeling markedly limits apoptosis in infected cells and facilitates efficient SFTSV replication. These findings uncover a previously unrecognized viral strategy in which SFTSV hijacks host PPM1K-dependent mitochondrial signaling to evade apoptosis and promote replication.
- Severe fever with thrombocytopenia syndrome virus (SFTSV)
- , Apoptosis
- , Protein phosphatase
- , Mg²⁺/Mn²⁺ dependent 1K (PPM1K)
- , BAX–caspase-3 pathway

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Electronic Supplementary Material

10.1016j.virs.2026.09.010-ESM.docx