# Exploring transcriptomic and genomic differences between susceptible and resistant fetal pigs to maternal PRRSV infection at late gestation

## TL;DR

This study explores how fetal pigs differ genetically and in thymic gene activity when they are resistant or susceptible to a virus that affects swine reproduction and breathing.

## Contribution

The study identifies genetic and transcriptomic differences in fetal thymus tissue linked to PRRS susceptibility, including novel ieQTLs for genes involved in T cell development.

## Key findings

- CR and PR fetuses showed low viral loads despite maternal exposure, while VS and MS fetuses had high viral loads.
- VS and MS fetuses exhibited interferon response and downregulation of cell cycle and DNA repair pathways.
- Severe infection (MS) was associated with disrupted T cell development and downregulation of genes like TMEM98 and PTCRA.

## Abstract

Porcine reproductive and respiratory syndrome (PRRS) severely impacts global swine production. While studies have revealed host genetic factors and molecular mechanisms of fetal response to PRRSV infection, the relationship between fetal genotype, thymic transcription and PRRS susceptibility remains unclear. This study integrates genomic and thymic transcriptomic analyses of fetal pigs from a maternal PRRSV-2 challenge model. Fetuses were categorized by susceptibility to PRRS, following maternal inoculation at gestation day 84–86 into four groups: complete resistance (CR), partial resistance (PR), viable susceptible (VS), and meconium-stained susceptible (MS). CR and PR fetuses exhibited 0 or less than 4 viral loads in serum and thymus, respectively, despite maternal exposure, while VS and MS fetuses had high viral loads with MS showing signs of compromise. Thymic transcriptome analyses revealed a strong interferon response and downregulation of cell cycle and DNA repair pathways in VS and MS fetuses compared to CR and PR fetuses. Severe infection (MS) was further associated with downregulation of genes involved in early thymocyte development, suggesting disrupted T cell development in the thymus. Interaction expression quantitative trait loci (ieQTLs) were identified, where the association between genetic variants and expression levels of differentially expressed genes (DEGs) varied by fetal PRRS susceptibility. Notably, ieQTLs were identified for genes critical for T cell development, including TMEM98 (involved in Th1 cell differentiation) and PTCRA (expressed in early stages of thymocyte development). These findings highlight the complex interplay between fetal genotype, thymic gene expression, and PRRS susceptibility, offering potential genetic markers for breeding programs for replacement gilts.

The online version contains supplementary material available at 10.1186/s13567-025-01621-w.