Comparative Transcriptomics Reveals Novel and Differential Circular RNA Responses Underlying Interferon-Mediated Antiviral Regulation in Porcine Alveolar Macrophages
Year: 2025
Type: article
Abstract: Porcine Reproductive and Respiratory Syndrome (PRRS) causes significant economic losses in the swine industry. Circular RNAs (circRNAs), a class of stable non-coding RNAs, are increasingly recognized as regulators in immune responses and host–virus interactions. This study investigated the genome-wide circRNA responses in porcine alveolar macrophages (PAMs), key cell targets of PRRSV, following treatment with a modified live virus (MLV) vaccine or two interferon (IFN) subtypes (IFN-α1, IFN-ω5). Using RNA sequencing, we identified over 1000 differentially expressed circRNAs across treatment groups, revealing both conserved and distinct expression profiles. Gene Ontology and KEGG pathway analyses indicated that circRNA-associated genes are significantly enriched in immune-related processes and pathways, including cytokine signaling and antiviral defense. Notably, IFN-ω5 treatment induced a pronounced circRNA response, aligning with its potent antiviral activity. We further explored the regulatory potential of these circRNAs by predicting miRNA binding sites, revealing complex circRNA-miRNA interaction networks. Additionally, we assessed the coding potential of differentially expressed circRNAs by identifying open reading frames (ORFs), internal ribosome entry sites (IRESs), and N6-methyladenosine (m6A) modification sites, suggesting a subset may undergo non-canonical translation. These findings provide a comprehensive landscape of circRNA expression in PAMs under different antiviral conditions, highlighting their potential roles as immune regulators and novel players in interferon-mediated antiviral responses, particularly downstream of IFN-ω5. This work contributes to understanding the non-coding RNA landscape in the PRRSV-swine model and suggests circRNAs as potential targets for future antiviral strategies.
Source: Viruses
DOI: 10.3390/v17101307
Authors: Jiuyi Li, Oluwaseun Adeyemi, Laura C. Miller, Yongming Sang
Institutions: Tennessee State University, Kansas State University
Language: English
Topic: Circular RNAs in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,137
OpenAlex ID: W4414615505