Non-coding RNA-mediated tug-of-war between emerging viruses and host antiviral defense: lessons from animal viruses

Emerging animal viruses pose persistent threats to livestock breeding and public health, underscoring the need for a deeper understanding of virus-host interactions. Nevertheless, the regulatory roles and conserved mechanisms of host non-coding RNAs (ncRNAs) during animal virus infections remain fragmented, and ncRNA-mediated mechanisms for emerging animal viruses are particularly poorly characterized, with no systematic collation or theoretical summarization available. Studies indicate that ncRNAs, including miRNAs, lncRNAs, and circRNAs, have emerged as important regulators of the interplay between animal viruses and their hosts. This review synthesizes evidence from eleven animal viruses covering swine, poultry, ruminant, feline, canine, and mink hosts, with emphasis on virus-induced changes in ncRNA expression and their antiviral or proviral functions. Across diverse virus-host systems, three recurring regulatory paradigms are identified: host antiviral defense, viral hijacking, and viral antagonism. Host cells can dynamically reshape their ncRNA expression to regulate host restriction factors, proviral host factors, and other ncRNAs, thereby influencing innate immune signaling, viral replication cycles, autophagy, apoptosis, and metabolic reprogramming. Conversely, animal viruses, including PEDV, PRRSV, PRV, SVA, AIV, ALV–J, NDV, BVDV, FHV–1, CIV, and MEV, have evolved sophisticated strategies to hijack host ncRNA networks or antagonize ncRNA-mediated antiviral immunity, and remodel the intracellular microenvironment to facilitate viral replication. These paradigms provide a unified theoretical system for understanding and predicting ncRNA–mediated regulatory mechanisms in emerging animal viruses. They also offer references for dissecting the pathogenic patterns of ASFV, SADS–CoV, and future unknown emerging viruses, as well as, for mining, screening, and identifying potential antiviral drug targets.