Pathogenic and transcriptomic differences among porcine reproductive and respiratory syndrome viruses from distinct lineages in piglets

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly recombinogenic pathogen that threatens global swine production. Multiple PRRSV lineages co-circulate in China, with lineage 1.8 being the predominant epidemic strain. However, the pathogenic characteristics and differences among strains from distinct lineages remain insufficiently studied. In this study, three novel recombinant PRRSV strains (GX-2428, GX-3264, and GX-5430) were isolated in Guangxi, China. Phylogenetic analysis of the ORF5 gene classified the three strains into lineage 3 (QYYZ-like), lineage 1.8 (NADC30-like), and lineage 1.5 (NADC34-like), respectively. Pathogenicity tests in piglets demonstrated that, compared with the control group, both GX-2428 and GX-3264 induced significant fever, whereas GX-5430 caused only a transient and milder febrile response. Infected piglets exhibited elevated levels of pro-inflammatory (IL-1β and TNF-α) and immunomodulatory cytokines (IL-4 and IL-10) compared to the control group. Postmortem analysis revealed that although viral shedding had ceased, high viral loads persisted in the lungs, tonsils, and lymph nodes of the infected piglets. Transcriptomic analysis of piglet lung tissues revealed that GX-5430 infection predominantly enriched pathways related to cellular transformation, signal transduction, and metabolic reprogramming. However, infections with GX-2428 or GX-3264 were significantly enriched in immune-related pathways, thereby inducing stronger immune activation and inflammatory responses. In conclusion, these findings highlight the recombination characteristics and lineage-specific pathogenic mechanisms of PRRSV, providing novel insights for the development of future prevention and control strategies.