Activation of the immune system is the pivotal event in the production of wasting disease in pigs infected with porcine circovirus-2 (PCV-2)

Porcine circovirus (PCV)-2, a newly described single-stranded circular DNA virus pathogen of swine is the cause of postweaning multisystemic wasting s yndrome (PMWS). In gnotobiotic piglets, PCV-2 infection alone produces asym ptomatic infection without evidence of overt PMWS. Gnotobiotic piglets infe cted with PCV-2 were injected with keyhole limpet hemocyanin in incomplete Freund's adjuvant (KLH/ICFA), and the effects on virus production and devel opment of PMWS were determined. In the first experiment, piglets were injec ted subcutaneously on the left hip and shoulder, and viral burden was asses sed in regional lymph nodes draining the injection sites and in contralater al lymph nodes 13-14 days after infection. Immune activation increased the number of virus antigen-positive cells in draining lymph nodes and increase d the amount of infectious virus recovered by 1-4 log(10). In a second expe riment, the effects of injections of KLH/ICFA with or without concurrent st imulation of peritoneal macrophages by intraperitoneal injections of thiogl ycollate broth on induction of PMWS was assessed. All immunized piglets dev eloped moderate to severe PMWS, whereas none of the piglets infected with P CV-2 alone developed PMWS. In PMWS-affected piglets, extensive replication of PCV-2 was documented by both immunocytochemistry and quantitative viral titrations. Thus, immune activation is a key component of the pathogenesis of PCV-2-associated PMWS in swine.