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

**Authors:** Jiuyi Li, Oluwaseun Adeyemi, Laura C. Miller, Yongming Sang

PMC · DOI: 10.3390/pathogens15010035 · 2025-12-26

## 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.

## Key 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.

## Linked entities

- **Proteins:** IFNA1 (interferon alpha 1)
- **Diseases:** porcine reproductive and respiratory syndrome (MONDO:0025494)
- **Species:** Sus scrofa (taxon 9823)

## Full-text entities

- **Genes:** MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}
- **Species:** Sus scrofa (pig, species) [taxon 9823], Porcine reproductive and respiratory syndrome virus (no rank) [taxon 28344]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12844857/full.md

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Source: https://tomesphere.com/paper/PMC12844857