Early Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Infection Induces Necroptosis in Immune Cells of Peripheral Lymphoid Organs.

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has caused huge economic losses to the pig industry in China. This study evaluated the damage to peripheral immune tissues in the early infection of HP-PRRSV, including the hilar lymph nodes, mandibulares lymph nodes, inguinales superficials lymph nodes, spleens, and tonsils. HP-PRRSV infection led to a reduction in CD4(+) and CD8(+) T cells, as well as CD19(+) B cells, in the tonsils. Additionally, CD163(+) macrophages and CD56(+) NK cells increased in all peripheral lymphoid organs, with NK cells migrating toward the lymphoid follicles. However, no significant changes were observed in CD11c(+) dendritic cells. RNA-seq analysis showed the down-regulation of T and B cell functions, while macrophage and NK cell functions were enhanced. Gene Ontology (GO) and KEGG pathway analysis indicated the up-regulation of necroptosis processes. Western blotting and immunofluorescence confirmed that HP-PRRSV induced PKR-mediated necroptosis in immunocytes. This study provides new insights into the effects of early HP-PRRSV infection on peripheral immune organs, highlighting dynamic shifts in immune cell populations, virus-induced immunosuppression, and the role of PKR-mediated necroptosis. These findings improve our understanding of the immunomodulation induced by PRRSV infection.