Mitochondrial dysfunction in PRRSV-2 infected macrophages

ABSTRACT: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is one of the most economically devastating viruses for the global swine industry. PRRSV has a known tropism for lung macrophages, where it causes impaired immune responses. This study evaluated the metabolic and immune profiles of primary porcine alveolar macrophages (PAM) and pulmonary intravascular macrophages (PIM) infected with different strains of PRRSV-2 isolated from North Carolina (NC) pig herds (NC134, NC18-9-7 referred to as NC174, NC20-1 referred to as NC144), and VR2232, a PRRSV-2 prototype strain. Primary enriched mononuclear phagocytes were infected ex vivo with NC134 and NC174, sorted, and the total RNA was used for a transcriptomic approach; additionally, gene expression was further validated by RT-qPCR and NanoString technology. Complementary functional assays with additional NC strains were used to further investigate the oxidative stress, mitochondrial and metabolic dysfunction induced by PRRSV-2 infection. PAM infected with both NC PRRSV-2 strains NC174 and NC134 showed similar transcriptomic profiles during the early stage of infection, with downregulation of genes involved in the oxidative phosphorylation and electron transport chain pathways. PIM infected with both NC174 and NC134 strains showed limited alteration in the transcriptomic profiles compared to uninfected cells. The genetic reprogramming matched the PRRSV-2 induced mitochondrial impairment observed in functional assays performed with Seahorse technology. Mitochondrial respiration displayed slightly different profiles between PIM and PAM infected with the different PRRSV-2 strains, with PAM showing a more substantial decrease in mitochondrial fitness compared to control cells. When reactive oxygen species (ROS) and nitric oxide (NO) production were evaluated, no differences were observed between PRRSV-2 infected PAM and PIM and control cells. These results provide valuable insights into the pathogenetic mechanism of different North Carolina PRRSV-2 strains, focusing on the alteration of mitochondrial function in lung macrophages during early infection and highlighting differences in lung macrophages responses to distinct PRRSV-2 strains

ORGANISM(S): Sus scrofa

PROVIDER: GSE304527 | GEO | 2025/10/17

REPOSITORIES: GEO