Pathogenesis of the more virulent form of systemic porcine circovirus type 2-associated disease
Porcine circovirus-associated disease (PCVAD) is considered a multifactorial disease since a variety of co-factors, including other infectious agents, seem to be necessary for full expression of clinical disease. To investigate if infection with ruminant pestiviruses is a co-factor in PCVAD, two experimental studies were conducted in pigs. In the first, two partially characterized virus preparations were inoculated into germ-free pigs either alone or with porcine circovirus type 2 (PCV2) group 2. These inocula were filtered tissue homogenates from diseased pigs known to contain either PCV2 group 1 (PCV2-1) and bovine viral diarrhea virus (BVDV) type 1-like virus, or BVDV type 1-like virus only without PCV2. A vaccination protocol against BVDV was tested as a possible measure to prevent development of clinical disease. One vaccinated, dually inoculated pig had acute respiratory distress followed by death at 21 days post infection. Lesions in this pig resembled the severe form of PCVAD recently observed in the field, suggesting a role of ruminant pestiviruses and/or vaccination in the development of this disease. In the second study, cesarean-derived, colostrum-deprived pigs were inoculated with PCV2-1 and a cytopathic strain of BVDV type 1 (cpBVDV-NADL) either alone or in combination. Clinical signs of PCVAD were seen in a single animal inoculated only with PCV2-1. This pig had growth retardation followed by acute respiratory distress and death 30 days post infection. Pulmonary lesions in this animal were similar to those seen in the pig that died in the first study. Infection with cpBVDV-NADL did not enhance PCV2-1 replication and lesion formation. This supports the theory that emergence of PCV2-1 in North America accounts for the change in the presentation of the disease seen since the fall of 2004.
The two pigs that died in these studies had multisystemic necrotizing vasculitis, one of the hallmark lesions of the severe form of PCVAD. Five additional pigs inoculated with PCV2-1 in the second study developed lymphohistiocytic and plasmacytic peri- and endarteritis. The pigs with acute vasculitis had abundant intralesional circoviral nucleic acid, and absent or low antibody titers to PCV2. In contrast, the pigs with lymphohistiocytic and plasmacytic vasculitis had circoviral nucleic acid in only rare non-affected vessels, and a high antibody titer against this virus. This suggests that the acute vasculitis is directly caused by the virus, whereas the chronic vasculitis is in part mediated by the immune response. The vascular alterations in pigs infected with PCV2 seemed to be dependent on host factors and on the group of the virus.