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

In this study, transcriptomic profiling identified PPM1K as a prominently induced host factor in SFTSV-infected THP-1 cells. 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, PPM1K dephosphorylates Bcl-2 at Ser248, decreases Bcl-2 ubiquitination, and stabilizes its anti-apoptotic activity, thereby suppressing 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