Pathogenicity and virulence of PRRSV: From regulated cell death reprogramming landscape and immune subversion to precision vaccinology

PRRSV remains a major challenge because pathogenicity arises from the convergence of rapid viral evolution, immune evasion, and maladaptive host responses rather than from isolated virulence determinants. This review synthesizes evidence from molecular and cellular studies, arguing that recurrent recombination, lineage turnover, and antigenic diversification continuously reshape viral fitness, tissue tropism, and vaccine efficacy. PRRSV suppresses interferon‑driven antiviral programs while rewiring inflammatory signaling and intertwined lytic and non-lytic regulated cell death cascades. The virus induces a phenotypic convergence akin to PANoptosis, notably marked by hyper-inflammatory pyroptotic responses in macrophages, which in turn facilitates immune dysfunction, delays the development of protective immunity, and contributes to persistent infection. We assess emerging intervention strategies, including consensus antigen design, rational attenuation, and nonreplicating platforms such as mRNA and protein nanoparticles. This framework explores regulated cell death pathways as a basis for identifying diagnostic biomarkers and developing precision vaccines for PRRSV.