Abstract
Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important diseases of swine worldwide. Since its first emergence in 1987 the PRRS virus (PRRSV) has become particularly divergent with highly pathogenic strains appearing in both Europe and Asia. However, the underlying mechanisms of PRRSV pathogenesis are still unclear. This study sets out to determine the differences in pathogenesis between subtype 1 and 3 strains of European PRRSV (PRRSV-I), and compare the immune responses mounted against these strains in both the blood and the local tissues, ie the mediastinal lymph nodes and the lung. Piglets were infected with 4 strains of PRRSV-I: Lelystad virus, 215-06 a British field strain, a vaccine strain DV and SU1-bel from Belarus. Blood was collected at various time points for viraemia to investigate viraemia and immune responses. Post-mortem examinations were performed at 3, 7 and 35 days post-infection (dpi), and cells were collected from the alveolar spaces and the lymph nodes. The subtype 3 SU1-bel strain displayed greater clinical signs and lung gross pathology scores compared with the subtype 1 strains. This difference did not appear to be caused by higher virus replication, as viraemia and viral load in broncho-alveolar lavage fluid (BALF) were lower in the SU1-bel group. Infection with SU1-bel induced an enhanced adaptive immune response with greater interferon (IFN)-γ responses and an earlier PRRSV-specific antibody response, in both blood and BALF, which correlated with gross pathology. Of particular note was the large influx of cytotoxic T cells and production of IFN-γ. On the other hand those pigs in the SU1-bel group, which had much less pathology, had the highest number of regulatory T cells and levels of the immunomodulatory cytokine Interleukin-10. The results of this study indicate that the immune response has an important role in the pathogenesis of PRRSV infection. Although these enhanced immune responses clear virus from the serum and BALF more quickly than responses seen in other strains, if these responses go unchecked, as they seem to in this case, it can have disastrous consequences for the animal. It may be possible to look at which factors are leading to this viral clearance and enhanced cellular immune response and use this data to perhaps devise a new vaccine that can monopolise on these mechanisms without causing the complications observed here.