Comparative Transcriptomics Reveals Novel and Differential Long-Noncoding RNA Responses Underlying Interferon-Mediated Antiviral Regulation in Porcine Alveolar Macrophages

TL;DR

This study explores how long non-coding RNAs in pig lung cells respond to a virus and interferons, revealing new insights into antiviral immunity.

Contribution

The study provides the first genome-wide analysis of lncRNA responses in porcine alveolar macrophages to PRRSV and interferons.

Findings

Over 2000 lncRNAs were found to be differentially expressed in response to PRRSV and interferons.

IFN-ω5 induced the most extensive transcriptional changes in lncRNA expression.

lncRNAs are involved in key immune pathways like chemokine signaling and mTOR.

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to the global swine industry. Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of antiviral immunity, but their roles in porcine alveolar macrophages (PAMs)—the primary target of PRRSV—remain poorly characterized. This study presents a genome-wide analysis of lncRNA expression in PAMs stimulated with a PRRS modified live virus (MLV) vaccine and two type I interferons, IFN-α1 and IFN-ω5. Whole-transcriptome sequencing identified over 2000 differentially expressed lncRNAs, with IFN-ω5 inducing the most extensive transcriptional reprogramming. Weighted gene co-expression network analysis (WGCNA) revealed interferon-specific lncRNA-mRNA modules, and functional enrichment showed these lncRNAs are involved in key immune and metabolic pathways, including chemokine signaling, MAPK, and mTOR. Our findings establish a comprehensive landscape of lncRNA regulation in PAMs, highlighting their role in fine-tuning the antiviral responses and suggesting novel targets for interferon-based antiviral interventions against PRRSV.

Figures