Immunopathogenesis of lung lesions induced by the highly virulent Rosalía strain of PRRSV-1 circulating in Spain since 2020

Highly virulent porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) strains, such as the Rosalía strain, continue to emerge in the swine industry. The mechanisms by which these strains induce lung pathology are not clearly understood. This study aimed to characterise the lung histopathological lesions and immune responses induced by the highly virulent Rosalía strain in experimentally infected pigs. Infected animals developed severe lung lesions, including extensive interstitial pneumonia, multifocal proliferative and necrotising pneumonia (PNP), and to a lesser extent, bronchopneumonia. Marked expression of von Willebrand factor (vWF) and reactive morphological changes in endothelial cells was observed, suggesting endothelial activation and increased vascular permeability which contributed to local inflammation. Throughout the course of infection, dynamic shifts in immune cell populations were observed. At 10 days post-infection (dpi), lung infiltrate was dominated by T cells and calprotectin⁺ myeloid-like cells, with a moderate presence of CD20⁺ cells, alongside a marked depletion of CD163⁺ pulmonary alveolar macrophages. Interestingly, CD163⁺ septal macrophages infiltrated areas around PNP and bronchopneumonia lesions, with several cells displaying spindle-shaped morphology. By 35 dpi, there was a replenishment of CD163⁺ cells and a significant increase in CD20⁺ cells, indicating a shift from an early innate to an adaptive immune response. The presence of tertiary lymphoid structures (TLS) with abundant CD20⁺ cell aggregates at this stage further supports sustained local immune activation. Our findings highlight immunopathological mechanisms underlying the severity of disease caused by the highly virulent Rosalía PRRSV-1 strain, characterised by severe lung immune dysregulation, macrophage depletion, endothelial activation, and delayed B-cell lymphoid response.