Opposing fates: a bipolar cellular model for FMDV replication shaped byCheavy-ion mutagenesis.

Abstract

INTRODUCTION: By pioneering the use of an 80 MeV/uCheavy-ion beam for mutagenesis, we have engineered a stably polarized BHK-21 cell model for FMDV replication. METHODS: This approach yielded two distinct clones: a highly antiviral line (BHK-5) and a highly proviral line (BHK-7). Multi-omics analyses were employed to investigate the mechanisms driving these divergent phenotypes. RESULTS: The divergent phenotypes stem from a profound reprogramming of host transcriptional networks. The antiviral BHK-5 clone exhibits a pre-activated innate immune state, leveragingsignaling for a rapid interferon response and viral clearance via autophagy. In stark contrast, the proviral BHK-7 clone enhances glycolysis and activates the PI3K-Akt pathway to suppress-mediated immunity and hijack thecell cycle phase, forming organized "virus factories." At the core of this reprogramming lies a systemic remodeling of transcription factor circuits, particularly within the Runt andzinc-finger families. DISCUSSION: Our work demonstrates thatCheavy-ion mutagenesis can rewire the host immunity-metabolism-cell cycle axis to dictate infection outcomes, providing a powerful framework and cellular toolkit for developing high-yield vaccine substrates and novel antiviral strategies.