Role of p38Alpha MAPK in Monkeypox Virus Replication and Neuroinvasion: Implications for Therapeutic Targeting

The mechanisms underlying monkeypox virus (MPXV)-induced neural injury remain unclear. Using non-human primate models, iPSC-derived neural cells, transcriptomic analysis, and CRISPR screening, our study identifies p38 MAPK as a central regulator of MPXV replication and neuroinflammation. It promotes viral maturation via viral protein modification and evades immunity by suppressing interferon signaling. p38 MAPK inhibitors effectively block viral proliferation, offering a promising broad-spectrum therapeutic target for poxvirus infections.