Morphologic studies of the pathogenesis of naturally occurring porcine circovirus type 2 diseases in pigs

This Ph.D. thesis presents different aspects of porcine circovirus diseases (PCVDs), based upon work performed at The Faculty of Life Sciences, University of Copenhagen, Denmark and at The National Veterinary Institute, Technical University of Denmark. The introduction, chapter 1, briefly presents the background and objectives of this study. Chapter 2 describes different aspects of porcine circovirus type 2 (PCV2), including molecular biology, genotypes, other closely related circoviruses and also the pathogenesis of PCV2 infections. Furthermore, the different porcine circovirus diseases (PCVDs) and experimental models of PCVDs are reviewed. In chapter 3, the results achieved by the research are presented as four manuscripts (I-IV): Manuscript I is focussed on the presence of PCV2 and viral replication, in the bone marrow and thymus of experimentally infected pigs and pigs naturally affected by postweaning multisystemic wasting syndrome (PMWS). By in situ hybridization (ISH) virus and viral replication was detected, mainly in histiocyte-like cells, in both organs of the PMWSaffected pigs. However, there was no evidence that bone marrow or thymus is especially important in regard of PCV2 replication. In manuscript II the occurrence and tissue distribution of PCV2 is examined, by immunohistochemistry (IHC) of lungs, kidneys, lymph nodes and spleen from slaughtered Danish finishing pigs with or without bronchopneumonia. Detection of PCV2 could not be related to lesions or PCVD. The virus was mainly detected in lymph nodes in association with follicular dendritic cells, which were identified by IHC. Whether this finding represents subclinical or persistent infection, or a status after PCV2 infection with innocent storage of antigen, remains unclear. Manuscript III focuses on the progression and diagnostics of an outbreak of naturally occurring PCV2 associated reproductive failure in a Danish herd. In stillborn and Summary VIII mummified foetuses PCV2 was detected mainly in the heart and bone marrow, by IHC, and replication was detected in myocardiocytes, by ISH. The study showed that measurements of total immunoglobulin G in foetuses are not very reliable as indication of intrauterine infection with PCV2. Furthermore, real-time polymerase chain reaction proved to be better for the detection of PCV2 in infected foetuses, compared to IHC, as PCV2 only was detected early in the outbreak by the latter method. • Manuscript IV is an update on the pathology and pathogens present in porcine respiratory disease complex (PRDC) in Danish finishing pigs. Multiple pathogens were detected, including PCV2, confirming the previously reported pathogen profile and multifactorial aetiology of PRDC. The histopathology was very variable and no clear-cut associations were detected between specific pathogens and histological lesions. In chapter 4, the achieved results are discussed and the future perspectives are addressed, and the thesis is closed with a summary of the drawn conclusions.