Porcine reproductive and respiratory syndrome associated with a recombinant virus between two commercial modified-live vaccine strains.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major cause of economic losses in the global swine industry, and the emergence of recombinant strains further complicates control efforts, particularly where modified-live vaccines (MLVs) are used. In March 2024, a commercial farrow-to-finish farm in Okinawa Prefecture, Japan, experienced a PRRS outbreak characterized by increased rates of preterm farrowing and stillbirths despite routine vaccination with a PRRS MLV. PRRSV isolated from an aborting sow, designated KU-OKN3, was subjected to whole-genome sequencing. Genomic analyses revealed that KU-OKN3 has a mosaic genome structure resulting from recombination between two distinct MLV strains: ORF2-ORF6 showed high nucleotide identity to one MLV strain, whereas ORF1b was more closely related to another. Notably, ORF5-based genotyping alone failed to detect the extensive recombination, underscoring the limitations of single-gene analyses for genetic characterization of PRRSV field strains. KU-OKN3 replicated efficiently in porcine alveolar macrophage-derived PAM-T43 cells at levels comparable to those of the parental MLV strains. In contrast, KU-OKN3 did not replicate productively in African green monkey kidney MA-104 cells, whereas both parental strains replicated efficiently, indicating distinct biological properties despite its vaccine-vaccine ancestry. Cytokine and chemokine profiling of infected PAM-T43 cells revealed increased IL-10 and IL-1α production, accompanied by suppression of IL-8 and IL-1Ra, with KU-OKN3 showing only a subtle increase in IL-8. Collectively, these findings demonstrate that vaccine-vaccine recombinant PRRSVs can emerge under field conditions and be associated with clinical outbreaks, highlighting the need for whole-genome surveillance and coordinated control strategies.