Refining genetic classification of global porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) and investigating their geographic and temporal distributions.

Porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) primarily circulates in Europe but is also detected in North America and Asia. Based on ORF5 sequences, previous studies classified PRRSV-1 into four subtypes. Subtype 1 was further classified into 12 clades (A-L) or into three lineages with lineage 1 including clades 1A-1G and lineage 3 including clades 3A-3G, but the systems are inconsistent and have not been adopted. In this study, we proposed a statistically supported PRRSV-1 genetic classification system based on 10,446 global PRRSV-1 ORF5 sequences spanning 1991-2023. We replaced the colloquial "subtype" designation with "lineage" to reflect evolutionary history and, subsequently, PRRSV-1 was classified into four lineages (L1-L4) with L1 including 18 sublineages (L1.1 to L1.18). The proposed classification system is flexible and may be amended if additional lineages, sublineages, or more granular classifications are needed to reflect contemporary PRRSV-1 detections and evolution. Geographic distributions of PRRSV-1 at lineage and sublineage levels were distinct, with L1 globally distributed and L2, L3 and L4 more restricted. Temporal dynamic changes in some countries were quantified. Classification and ORF5 nucleotide identity of six commercial PRRSV-1 vaccines to each lineage and sublineage and detection frequency of vaccine-like viruses were determined. The phylogenies based on whole-genome and ORF5 sequences demonstrated slightly different tree topologies. Recombination of PRRSV-1 was observed at within-sublineage and between-sublineage levels. A set of ORF5 reference sequences representing the refined classification is available for future diagnostic and epidemiological applications. This study provides a benchmark delineating the current genetic diversity of PRRSV-1 and introduces a refined classification system to support the global standardization and application of ORF5-based genetic classification for PRRSV-1.