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

Abstract

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 (7.57 ϫ 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 (12.5%), 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 U.S. 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 identi- Citation Palinski R, Piñeyro P, Shang P, Yuan F, Guo R, Fang Y, Byers E, Hause BM. 2017. A novel porcine circovirus distantly related to known circoviruses is associated with porcine dermatitis and nephropathy syndrome and reproductive failure. J Virol 91:e01879-16.

A commercial porcine circovirus (PCV) type 2a-based vaccine reduces PCV2d viremia and shedding and prevents PCV2d transmission to naïve pigs under experimental conditions

“…It has been suggested that excessive PCV2 antibody titers may trigger the development of PDNS [38]. In addition, other etiological agents such as PRRSV and torque teno virus [39] or PCV3 [40] have also been proposed as triggers or causative agents in PDNS. The PDNS-affected pig in this study had no detectable PCV2 antibody titer at challenge and the titer increased towards a low positive level over the following weeks.…”

Establishment of a sensitive TaqMan‐based real‐time PCR assay for porcine circovirus type 3 and its application in retrospective quarantine of imported boars to China

“…Of note, three sequences of capsid gene from the United Kingdom and five sequences from the United States detected by this study showed 100% identity to PCV3/KU‐1602 from Korea (Kwon et al . ) and PCV3 29160 from the United States (Palinski et al ., ).…”

“…We did not compare our method with another important real‐time PCR established by Palinski et al . (). due to technical difficulties in synthesis of their designed probe.…”

Diagnostic accuracy of two DNA‐based molecular assays for detection of porcine circovirus 3 in swine population using Bayesian latent class analysis

“…More recently, a new swine circovirus species named PCV‐3 has been described (Palinski et al . ). Its genome includes two major open reading frames (ORFs), ORF1 and ORF2, located in different strands of the viral replicative form, oriented in opposite direction and encoding the replicase (Rep) and capsid (Cap) proteins, respectively (Palinski et al .…”

“…PCV‐3 has been reported in North and South America (Palinski et al . ; Tochetto et al . ), Asia (Kwon et al .…”