Porcine Circovirus Type 2-Associated Cerebellar Vasculitis in Postweaning Multisystemic Wasting Syndrome (PMWS)-Affected Pigs

Abstract

Porcine circovirus type 2 (PCV2) is associated with several syndromes in growing pigs, including postweaning multisystemic wasting syndrome and porcine dermatitis and nephropathy syndrome. In the present study, a previously undescribed neurovascular disorder associated with a PCV2 infection is described. Sixteen pigs showed clinical signs of wasting and neurologic deficits. Acute hemorrhages and edema of cerebellar meninges and parenchyma due to a necrotizing vasculitis resulted in degeneration and necrosis of the gray and white matter. Few to numerous PCV2 DNA and antigen-bearing endothelial cells were detected in affected areas of the brain using in situ hybridization and immunohistochemistry. Conventional histochemical stains, as well as the detection of caspase 3 activity and DNA strand breaks by the terminal transferase dUTP nick end labeling assay, showed numerous apoptotic endothelial cells in the vascular lesions observed. Sequencing of various brain-derived PCV2-specific amplicons revealed a strong identity between different isolates and an 89 to 100% identity to previous isolates. The phylogenetic tree showed that there was no clustering of isolates correlating to clinical signs or geographic distribution. This previously undescribed PCV2-associated neurologic disease has features of both postweaning multisystemic wasting syndrome and, to a lesser extent, porcine dermatitis and nephropathy syndrome. The available evidence suggests that direct virus-induced apoptosis of endothelial cells plays a role in the pathogenesis of this unusual PCV2-associated cerebellar vasculitis.

Association of Porcine Circovirus Type 2 With Vascular Lesions in Porcine Pneumonia

“…4,13,22,23 PCV2 antigen was detected in endothelial cells, smooth muscle cells of the tunica media, infiltrating leukocytes, intravascular and perivascular macrophages, and intravascular monocytes in the present study and in previous reports. 4,11,[13][14][15]17,[21][22][23] Furthermore, intimal spindle cell proliferation was found in a few cases (data not shown) and was recently reported in a cesarean-derived/colostrum-deprived pig inoculated with PCV2b. 13 No correlation was found between the number of infected cells and the presence or severity of the vascular lesions, suggesting a host immune system-induced alteration rather than a direct PCV2-induced lesion.…”

“…18 Involvement of the vasculature in PCV2 infection has been reported. 2,4,13,17,22,23 In vitro endothelial activation and diminished coagulation time in swine naturally infected with PCV2 were demonstrated. These changes and the presence of PCV2 antigen in endothelial cells of naturally infected pigs pointed to PCV2 infection as the cause of vascular lesions.…”

“…2,4,13,17,22,23 A marked increase in the incidence and severity of PCVAD was observed in eastern Canada in 2004 and was attributed to the emergence of the PCV2b virus cluster.…”

Singular PCV2a or PCV2b infection results in apoptosis of hepatocytes in clinically affected gnotobiotic pigs

“…Studies conducted by several research groups have identified apoptosis by TUNEL assay (Shibahara et al, 2000;Krakowka et al, 2004;Mandrioli et al, 2004;Resendes et al, 2004a;Seeliger et al, 2007) and CCasp3 IHC (Resendes et al, 2004a,b;Seeliger et al, 2007) in conventional, clinically-affected pigs (Rosell et al, 1999(Rosell et al, , 2000b. A recent investigation on conventional pigs using the TUNEL assay, CCasp3 IHC and PCV2 in situ hybridization (ISH) provided evidence of virus-induced apoptosis in endothelial cells in pigs diagnosed with PCV2-associated cerebellar vasculitis (Seeliger et al, 2007). Similarly, a study using conventional clinically-affected pigs, the TUNEL assay and PCV2 ISH found that diminished lymphoid cell proliferation was the actual cause of cell depletion (Mandrioli et al, 2004).…”

Vascular lesions and pneumonia in a pig fetus infected by porcine circovirus type 2

“…In this study, microscopic lesions were found only in the lungs, where multinucleated giant cells and prominent vascular lesions were detected first, with the parallel presence of nonsuppurative pneumonia. The presence of multinucleated giant cells in pig fetuses has so far been described only in the lymphoid organs (Opriessnig and Langohr, 2012) and vascular lesions have been reported only in growing and adult pigs with PMWS or PRDC (Opriessnig et al, 2006;Correa et al, 2007;Seeliger et al, 2007;Langohr et al, 2010;Szeredi et al, 2012;Resendes and Segalés, 2014). The presence of large amounts of PCV2 antigen in and around the blood vessels of different fetal organs suggests that the vascular system may be important in the pathogenesis of fetal PCV2 infection as well.…”