Porcine circovirus 3 (PCV-3) was discovered in 2015 using next-generation sequencing (NGS) methods. Since then, the virus has been detected worldwide in pigs displaying several clinical-pathological outcomes as well as in healthy animals. The objective of this review is to critically discuss the evidence existing so far regarding PCV-3 as a swine pathogen. In fact, a significant number of publications claim PCV-3 as a disease causal infectious agent, but very few of them have shown strong evidence of such potential causality. The most convincing proofs of disease association are those that demonstrate a clinical picture linked to multisystemic lymphoplasmacytic to lymphohistiocytic perivascular inflammation and presence of viral nucleic acid within these lesions. Based on these evidence, individual case definitions for PCV-3reproductive disease and PCV-3-systemic disease are proposed to standardize diagnostic criteria for PCV-3-associated diseases. However, the real frequency of these clinical-pathological conditions linked to the novel virus is unknown, and the most frequent outcome of PCV-3 infection is likely subclinical based on its worlwide distribution.

Porcine circovirus 3 (PCV-3) has been widely detected in healthy and diseased pigs; among different pathologic conditions, the strongest evidence of association comes from reproductive disease cases. However, simple viral detection does not imply the causality of the clinical conditions. Detection of PCV-3 within lesions may provide stronger evidence of causality. Thus, this study aimed to assess the frequency of PCV-3 detection in tissues from fetuses/stillborn piglets in cases of reproductive problems in domestic swine, as well as the histopathologic assessment of fetal tissues. Fetuses or stillborn piglets from 53 cases of reproductive failure were collected and analyzed by PCV-3 qPCR. The presence of porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus 2 (PCV-2), and porcine parvovirus 1 (PPV1) was also checked. PCV-3 qPCR positive samples with a high viral load were tested by PCV-3 in situ hybridization (ISH), sequenced, and phylogenetically analyzed. PCV-3 DNA was detected in 18/53 (33.9%) reproductive failure cases and in 16 of them PCV-3 was the only pathogen found. PCV-2 DNA was found in 5/53 (9.4%), PRRSV RNA in 4/53 (7.5%) and PPV1 was not detected. Four out of the six PCV-3 qPCR-positive cases with Ct value <30 were positive when tested by ISH. In these samples, PCV-3 was detected within mild histopathologic lesions, such as arteritis and periarteritis in multiple tissues. The present work emphasizes the need to include PCV-3 as a potential causative agent of reproductive failure in swine.

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