Porcine circovirus-associated disease (PCVAD) is clinically manifested by postweaning multisystemic wasting syndrome (PMWS), respiratory and enteric disease, reproductive failure, and porcine dermatitis and nephropathy syndrome (PDNS) Porcine circovirus 2 (PCV2) is an essential component of PCVAD, although an etiologic role in PDNS is not well established Here, a novel circovirus, designated porcine circovirus 3 (PCV3), was identified in sows that died acutely with PDNS-like clinical signs The capsid and replicase proteins of PCV3 are only 37% and 55% identical to PCV2 and bat circoviruses, respectively Aborted fetuses from sows with PDNS contained high levels of PCV3 (757 × 10 7 genome copies/ml), and no other viruses were detected by PCR and metagenomic sequencing Immunohistochemistry (IHC) analysis of sow tissue samples identified PCV3 antigen in skin, kidney, lung, and lymph node samples localized in typical PDNS lesions, including necrotizing vasculitis, glomerulonephritis, granulomatous lymphadenitis, and bronchointerstitial pneumonia Further study of archived PDNS tissue samples that were negative for PCV2 by IHC analysis identified 45 of 48 that were PCV3 positive by quantitative PCR (qPCR), with 60% of a subset also testing positive for PCV3 by IHC analysis Analysis by qPCR of 271 porcine respiratory disease diagnostic submission samples identified 34 PCV3-positive cases (125%), and enzyme-linked immunosorbent assay detection of anti-PCV3 capsid antibodies in serum samples found that 46 (55%) of 83 samples tested were positive These results suggest that PCV3 commonly circulates within US swine and may play an etiologic role in reproductive failure and PDNS Because of the high economic impact of PCV2, this novel circovirus warrants further studies to elucidate its significance and role in PCVAD
 IMPORTANCE While porcine circovirus 2 (PCV2) was first identified in sporadic cases of postweaning multisystemic wasting syndrome in Canada in the early 1990s, an epidemic of severe systemic disease due to PCV2 spread worldwide in the ensuing decade Despite being effectively controlled by commercial vaccines, PCV2 remains one of the most economically significant viruses of swine Here, a novel porcine circovirus (PCV3) that is distantly related to known circoviruses was identified in sows with porcine dermatitis and nephropathy syndrome (PDNS) and reproductive failure PCV2, which has previously been associated with these clinical presentations, was not identified High levels of PCV3 nucleic acid were observed in aborted fetuses by quantitative PCR, and PCV3 antigen was localized in histologic lesions typical of PDNS in sows by immunohistochemistry (IHC) analysis PCV3 was also identified in archival PDNS diagnostic samples that previously tested negative for PCV2 by IHC analysis The emergence of PCV3 warrants further investigation

A Novel Porcine Circovirus Distantly Related to Known Circoviruses Is Associated with Porcine Dermatitis and Nephropathy Syndrome and Reproductive Failure

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus–associated disease (PCVAD). The virus preferentially targets the lymphoid tissues, which leads to lymphoid depletion and immunosuppression in pigs. The disease is exacerbated by immunostimulation or concurrent infections with other pathogens. PCV2 resides in certain immune cells, such as macrophage and dendritic cells, and modulates their functions. Upregulation of IL-10 and proinflammatory cytokines in infected pigs may contribute to pathogenesis. Pig genetics influence host susceptibility to PCV2, but the viral genetic determinants for virulence remain unknown. PCV2 DNA and proteins interact with various cellular genes that control immune responses to regulate virus replication and pathogenesis. Both neutralizing antibodies and cell-mediated immunity are important immunological correlates of protection. Despite the availability of effective vaccines, variant strains of PCV2 continue to emerge. Although tremendous progr...

Porcine Circovirus Type 2 (PCV2): Pathogenesis and Interaction with the Immune System

The natural history of porcine circovirus type 2: From an inoffensive virus to a devastating swine disease?

In pigs, three circovirus species within the genus Circovirus have been identified so far, including the non-pathogenic Porcine circovirus 1 (PCV1), the pathogenic Porcine circovirus 2 (PCV2) and the recently identified Porcine circovirus 3 (PCV3). In April 2019, a new circovirus with a distinct relationship to other circoviruses was identified in several pigs with severe clinical disease in Hunan province, China. The size of the viral genome, tentatively designated as porcine circovirus type 4 (PCV4), is 1,770 nucleotides (nt). PCV4 shows the highest genomic identity to mink circovirus (66.9%) and has identities of 43.2%-51.5% to the other PCV genomes. Two major genes, a replicase (Rep) gene spanning 891 nt and a capsid (Cap) gene spanning 687 nt, were predicted. Furthermore, a TaqMan® real-time polymerase chain reaction (PCR) targeting the replicase gene was developed to investigate the prevalence of PCV4 in 187 clinical samples from Hunan province, China. The results revealed an overall PCV4 prevalence of 12.8%, with the highest positive rates in nasal swabs (28.5%, 6/21) followed by serum samples (13.4%, 11/82). The clinical significance and pathogenesis of this virus needs further investigation.

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Novel circovirus species identified in farmed pigs designated as Porcine circovirus 4, Hunan province, China.

We characterized the complete genome of a novel dog circovirus (DogCV) from the liver of a dog with severe hemorrhagic gastroenteritis, vasculitis, and granulomatous lymphadenitis. DogCV was detected by PCR in fecal samples from 19/168 (11.3%) dogs with diarrhea and 14/204 (6.9%) healthy dogs and in blood from 19/409 (3.3%) of dogs with thrombocytopenia and neutropenia, fever of unknown origin, or past tick bite. Co-infection with other canine pathogens was detected for 13/19 (68%) DogCV-positive dogs with diarrhea. DogCV capsid proteins from different dogs varied by up to 8%. In situ hybridization and transmission electron microscopy detected DogCV in the lymph nodes and spleens of 4 dogs with vascular compromise and histiocytic inflammation. The detection of a circovirus in tissues of dogs expands the known tropism of these viruses to a second mammalian host. Our results indicate that circovirus, alone or in co-infection with other pathogens, might contribute to illness and death in dogs.

Circovirus in Tissues of Dogs with Vasculitis and Hemorrhage

Clinical signs and pathological features are still the corner-stones to suspect and diagnose overt disease associated with PCV2 infection. The clinico-pathological scope of this viral infection has been expanded over time. From the initial description of postweaning multisystemic wasting syndrome, some enteric, respiratory and reproductive disorders have been subsequently linked with PCV2. Porcine dermatitis and nephropathy syndrome, an immunocomplex disease, has also been associated with infection by this virus. All together, these conditions have been grouped under the name of porcine circovirus diseases (PCVD) or porcine circovirus associated diseases (PCVAD). The precise mechanisms by which a PCV2 infected pig develops a PCV2 subclinical infection or a clinical PCVD/PCVAD are still to be fully elucidated, but inferences based upon clinical, gross and histologic findings from field cases of disease have been useful to suggest the pathogenesis of this viral infection. The objective of the present review is to update the current knowledge on the clinical and pathological scope of PCV2 infections, as well as on their diagnosis. Moreover, a proposal on a unified PCVD/PCVAD terminology and clearly defined diagnostic criteria for these conditions are also given. © 2011 Elsevier B.V. All rights reserved.

oaquim Segalésa

Papers

Porcine circovirus type 2 (PCV2) infections: Clinical signs, pathology and laboratory diagnosis