Epsilon Open Archive

Abstract

Porcine circovirus type 2 (PCV2) causes postweaning multisystemic wasting syndrome (PMWS) in growing pigs but generally requires the presence of other infectious or non-infectious factors to produce the full clinical expression of disease. These factors remain to be identified, but management routines, concurrent infections and maternal immunity are thought to influence the risk for PMWS outbreak in swine herds. Pigs presenting with PMWS develop severe immunosuppression and the work of this thesis focuses on the interaction between PCV2 and the immune system of the pig in vivo and in vitro. Development of PMWS was studied in models for experimental infection in young pigs using coinfections with porcine parvovirus (PPV) or Escherichia coli. Three-day-old colostrum-deprived pigs infected with PCV2 and PPV developed severe PMWS, and a possible role for interleukin 10 as well as impaired production of antibodies to PCV2 in the development of disease was observed. Four-week-old colostrum fed pigs infected with PCV2 in combination with E. coli did not develop clinical disease, but alterations of functions of immune cells were observed ex vivo and could be related to the presence of PCV2. DNA from virus and bacteria can act modulatory on immune cells through the interaction between unmethylated CpG motifs and toll-like receptor (TLR) 9. Five sequences with interferon (IFN) alpha-modulatory activity were identified in the genome of PCV2, and the inhibitory characteristics of one of these (ODN PCV2/1) were studied further in vitro. The ODN was an efficient inhibitor of IFN-α production induced in porcine peripheral blood mononuclear cells (PBMCs) by other DNA ODNs as well as bacterial or viral DNA, but could not influence the IFN-α production induced by synthetic or viral RNA. The inhibition was dependent on the ability of ODN PCV2/1 to form secondary structures, but did not require the presence of an unmethylated CpG motif. ODN PCV2/1 also inhibited the expression of mRNA for other porcine cytokines by PBMC stimulated in vitro. The presence of immunomodulatory sequences in the genome of PCV2 may contribute to evasive mechanisms utilized by the virus during persistent infection of immune cells and/or development of clinical disease.