SFTSV exploits PPM1K to inhibit apoptosis through the Bcl-2/BAX/Caspase-3 axis for efficient replication
- 1State 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
- 2State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150000, China
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.
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BibTeX
@article{wang2026sftsv,
title = {{SFTSV exploits PPM1K to inhibit apoptosis through the Bcl-2/BAX/Caspase-3 axis for efficient replication}},
author = {Qianruo Wang and Baoyan Wang and Penghui Liu and Yuanyuan Li},
journal = {Virologica Sinica},
year = {2026},
month = sep,
doi = {10.1016/j.virs.2026.09.010},
url = {https://doi.org/10.1016/j.virs.2026.09.010},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - SFTSV exploits PPM1K to inhibit apoptosis through the Bcl-2/BAX/Caspase-3 axis for efficient replication
AU - Qianruo Wang
AU - Baoyan Wang
AU - Penghui Liu
AU - Yuanyuan Li
PY - 2026
DA - 2026/09/24
JO - Virologica Sinica
DO - 10.1016/j.virs.2026.09.010
UR - https://doi.org/10.1016/j.virs.2026.09.010
AB - 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.
SN - 1674-0769
SN - 1995-820X
ER -