Macro-scale resolution of recombination landscapes and structural adaptations in global PRRSV-2: A 35-year genomic retrospective

Porcine reproductive and respiratory syndrome virus 2 (PRRSV-2) exhibits high genetic diversity and frequent recombination, yet its global evolutionary mechanisms remain poorly defined. Analyzing over 42,000 sequences spanning 1990–2025, we quantified a significant geographical shift in genomic surveillance toward China, which has accounted for 56.01% of global public records since 2018. Between 2014 and 2017, modular recombination emerged as a primary driver of global genomic diversification, with Lineage 1C (L1C) serving as the primary recipient of diverse genomic segments. Specifically, the L1C-R8E-mosaic group has emerged to comprise 47.7% of recent recombinants, featuring a Lineage 8E (L8E)-derived replicase core integrated with heterologous antigenic shells, the surface protein clusters that primarily drive host immune selection. High-resolution mapping identified nonstructural protein 7 ( nsp7) gene as a primary recombination hotspot (417.0 breakpoints/kb). Our data suggest that nsp7 may act, reflecting the balance between core structural stability and peripheral adaptive plasticity, as a primary recombination hotspot, a hypothesis that warrants further experimental validation to confirm the biological impact of this high breakpoint density. Furthermore, we propose a Core-Periphery Trade-off Model for nucleotide evolution: core modules ( nsp9 , nsp12 ) undergo guanine-cytosine (GC) enrichment to preserve structural integrity, while peripheral regions ( ORF3 ) exhibit progressive GC loss. Structural modeling via AlphaFold3 suggests that positive selection targets solvent-exposed loops, although these predictions still require validation by experimental structures. Within the entry machinery, our structural predictions suggest that adaptive mutations on glycoprotein 3 (GP3) and the glycoprotein 5-membrane (GP5-M) heterodimer are confined to the solvent-exposed periphery, remaining spatially segregated from the conserved receptor-binding core primarily anchored by glycoprotein 2a (GP2a). Similarly, in nonstructural protein 2 (Nsp2), adaptive sites are localized to conformational hinge points at the bases of flexible loops, which may potentially influence protein dynamics. These findings delineate the transition of PRRSV-2 into a modular evolutionary phase and provide a structure-guided framework for global surveillance and intervention strategies.