Experimental infection of pigs with European porcine reproductive and respiratory syndrome virus: correlations with pathology

Aims and objectives:

Based on previous work, a core hypothesis has been formulated as follows:  “Genetic variation between pig breeds and between different strains of PRRSV has functional consequences on the immune response to PRRSV and other secondary infections”.

This project will establish whether a vaccine-like PRRSV strain recently isolated from a clinical submission is able to infect pigs and cause disease under controlled conditions in vivo.  Furthermore we will compare the results to those obtained with other British and overseas isolates of differing pathogenicity, and the vaccine strain itself.  The response of two breeds of pigs will be compared, to better determine the combined effects of the host-pathogen interactions.  The project will generate samples for later use in various immunological assays in vitro, to reveal and compare the immune response and changes induced by PRRSV infection by different virus strains in different pig breeds.

Summary of findings:

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  ofPRRSV  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,  hich 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 responsehas an important role in thepathogenesis 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.