ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Veterinary and Zoonotic Infection
This article is part of the Research TopicUnveiling Host-Pathogen Interactions: Insights into Animal Cellular Immunity and Novel Diagnostics - Volume IIView all 24 articles
Opposing Fates: A Bipolar Cellular Model for FMDV Replication Shaped by 12C6+Heavy-Ion Mutagenesis
Provisionally accepted
- 1College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
- 2China Agricultural Vet Biology and Technology Co., Ltd, LANZHOU, China
- 3Institute of Modern Physics Chinese Academy of Sciences, Lanzhou, China
- 4Gansu Normal University for Nationalities, Hezuo, China
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By pioneering the use of an 80 MeV/u ¹²C⁶⁺ heavy-ion beam for mutagenesis, we have engineered a stably polarized BHK-21 cell model for FMDV replication. This approach yielded two distinct clones: a highly anti-viral, anti-viral line (BHK-5) and a highly pro-viral, pro-viral line (BHK-7). Multi-omics analyses revealed these divergent phenotypes stem from a profound reprogramming of host transcriptional networks. The anti-viral BHK-5 clone exhibits a pre-activated innate immune state, leveraging RIG-I/TLR signaling for a rapid interferon response and viral clearance via autophagy. In stark contrast, the pro-viral BHK-7 clone enhances glycolysis and activates the PI3K–Akt pathway to suppress TNF-mediated immunity and hijack the G2/M cell cycle phase, forming organized "virus factories." At the core of this reprogramming lies a systemic remodeling of transcription factor circuits, particularly within the Runt and C2H2 zinc-finger families. Our work demonstrates that ¹²C⁶⁺ heavy-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
Keywords: ¹²C⁶⁺ heavy-ion1, BHK-213, transcription factor4, FMDV (foot-and-mouth disease virus), BHK-21 cell line
Received: 28 Sep 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 Song, Cui, An, Li, Liang, Tao and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiangdong Song, 18298349782@163.com
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