Genetic Diversity and Temporal Shifts of Porcine Reproductive and Respiratory Syndrome Virus Type 2 (PRRSV-2) Strains in Japan (2020–2023): Evidence of Modified Live Vaccine Influence on Cluster Distribution

Background: Porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) remains a significant threat to swine production globally, including Japan. While the genetic diversity of PRRSV-2 has been reported previously, the potential association with modified live vaccines (MLV) is not well understood. This study aimed to characterize PRRSV-2 strains currently circulating in Japan and assess possible links with MLV. Methods: A total of 1,190-nucleotide open reading frame 5 sequences of PRRSV-2 were collected across Japan between 2020 and 2023, and phylogenetic analyses were performed to classify genetic clusters. Additionally, correlations between cluster distribution and MLV usage were examined, using sequences detected in the Kanto region. Results: Phylogenetic analysis revealed that 48.5% of the sequences belonged to Cluster III, with a median nucleotide identity of 90.5% to the Japanese reference strain EDRD-1. Notably, the sequence identity between the strains detected in this study and EDRD-1 was significantly lower than that of strains identified in 1992–1993 (p < 0.05). In the Kanto region, Cluster I and II variants, which exhibited high sequence homology to MLV strains, were exclusively detected on farms with a history of MLV usage. Furthermore, Cluster IV displayed substantial genetic divergence, suggesting it comprises a heterogeneous group of distinct lineages. Conclusions: These findings demonstrated the temporal changes in the genetic diversity of Cluster III and provided clear evidence that MLV usage directly influences PRRSV-2 cluster distribution, with Clusters I and II likely representing vaccine-origin viruses. The marked heterogeneity of Cluster IV also highlights the limitations of the current cluster-based classification.