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

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

Qianruo Wang ^a,b ,
Baoyan Wang ^a ,
Penghui Liu ^a ,
Yuanyuan Li ^{a
,,}

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
Available online: 24 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

Electronic Supplementary Material

10.1016j.virs.2026.09.010-ESM.docx
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