Pathogenicity and immune modulation of porcine circovirus 3.

Porcine circoviruses (PCVs) are members of the genus Circovirus of the family Circoviridae, and four species of PCVs have been discovered and named PCV1-PCV4, respectively. With the first report of PCV3 in America in 2016, the pathogenic variant was found to be associated with various clinical features, called porcine circovirus associated disease (PCVAD), including multisystemic inflammation, porcine dermatitis and nephropathy syndrome (PDNS), reproductive disorders, respiratory or digestive disorders. Increasing experimental data have shown that PCV3 is widespread around the world, but the failure of virus isolation and propagation has put obstacles in the way of PCV3 research. Moreover, a large number of reports demonstrate that PCV3 usually co-infects with other pathogens in pigs. Thus, whether PCV3 alone causes clinical manifestations needs to be fully discussed. In addition, the host cell immune response was activated during PCV3 infection, and PCV3-encoded proteins may regulate immune responses to facilitate its replication. An in-depth understanding of PCV3 pathogenesis and immune regulation strategies is critical for PCVAD prevention. In this review, the advances in pathogenicity and innate immune modulation of PCV3 were summarized, which could deepen the understanding of this virus and PCV3-related diseases.

A Retrospective Analysis of Porcine Circovirus Type 3 in Samples Collected from 2008 to 2021 in Mexico.

Porcine circovirus type 3 (PCV3) is a nonenveloped virus of the Circoviridae family. This virus has been identified in pigs of different ages and pigs with several clinical manifestations of the disease or even in apparently healthy pigs. While PCV3 was first reported in 2015, several retrospective studies have reported the virus before that year. The earliest report indicates that PCV3 has been circulated in swine farms since 1996. In this study, we evaluated the presence of PCV3 in samples collected in Mexico in 2008, 2015, 2020, and 2021. This study assessed PCV3 DNA by qPCR and antibodies against CAP protein by indirect ELISA. The results showed that PCV3 (DNA and anti-CAP antibodies) was detected in the samples collected from 2008 to 2021. The highest prevalence was in 2008 (100%), and the lowest was in 2015 (negative). Genetic analysis of ORF2 showed that the virus identified belonged to genotype a, as most of the viruses identified thus far. PCV3 was detected in samples from piglets with respiratory signs and growth retardation, sows with reproductive failure, or asymptomatic piglets and sows. Pigs with respiratory signs, growth retardation, or reproductive failure had a higher prevalence of antibodies and qPCR-positive samples. In conclusion, this study showed that PCV3 has been circulating in Mexico since 2008 and that PCV3 DNA and antibodies were more prevalent in samples from pigs with clinical manifestations of diseases.

Histopathological Changes and Inflammatory Response in Specific Pathogen-Free (SPF) with Porcine Circovirus Type 3 Infection.

Since the first report of PCV3 virus infection in 2016, it has been linked to multisystemic inflammation, reproductive failure, cardiac pathology, and clinical indications resembling porcine dermatitis and nephropathy syndrome (PDNS). However, the pathogenesis and clinical significance of PCV3 is still unclear. In this study, a PCV3 infection model was created using SPF pigs, and histopathology and fluorescence quantitative PCR were utilized to examine PCV3's pathogenicity. Reductions in body weight gain and fever were observed during this study. However, other clinical signs such as Dermatitis and Nephropathy Syndrome were not observed through the study. Viremia was detected in the PCV3-inoculated group from 17 days post-inoculation (p.i.) until the end of the study. Nasal shedding was detected from 21 to 35 dpi and fecal shedding was detected during 25-33 days and 39 days, respectively. Gross lesions and histological evaluation were detected in various tissues and organs, including the lung, heart, kidney, lymph nodes, spleen, liver, small intestine, and testis. The heart, lung, liver, kidney, lymph nodes, and spleen showed pathological changes. The pathological features include swelling, inflammation, cell degeneration, necrosis, and hemorrhage. The lesions are consistent with multisystemic inflammation. Tissue viral load results showed only heart, lung, liver, kidney, lymph nodes, and spleen was positive by qRT-PCR. Moreover, the pro-inflammation cytokines in serum increased a lot in the PCV3-inoculated group compared to the control group, demonstrating that the induced inflammation response may be the cause of tissue damage in PCV3-infection. This study demonstrated that PCV3 can produce mild pathological damage to multiple organs, especially multisystemic inflammatory cell infiltration and prolonged viremia, viral shedding in nasal secretions. This is the first in vivo characterization of PCV3 infection in the SPF piglets model using isolated PCV3 strain, and this is also the first time to show the gross and pathological lesion with all tissue and organs in the PCV3-inoculated group. Our findings might serve as a starting point for more investigation into PCV3's pathogenic mechanism.

Porcine circovirus 3 (PCV-3) variability: Is it in the virus or in the classification criteria?

The continuous discovery of new viruses during the last decades has increased the need for new classification approaches and rules. Currently, the International Committee on Taxonomy of Viruses classifies viruses up to the species level. However, because of the higher variability of most of these infectious agents, a below-species categorization is often required for proper epidemiological investigations. Unfortunately, variable criteria are typically proposed by different research groups, leading to misleading and poorly reproducible results. This scenario occurred for the recently identified Porcine circovirus 3. Although genotype definition standards had been defined by a group of experts in the field, recent articles have been published introducing new genotypes, whose classification rules are not reported. We therefore would like to stress the usefulness of defining and maintaining a common language to allow proper results comparison among groups. We consider the consensus opinion of a heterogeneous expert team as the most valuable approach. Nevertheless, if other approaches are proposed, the disclosure of the criteria and the comparison with previous literature should be deemed mandatory to allow effective results reproducibility, interpretation and sharing.

Porcine circoviruses in wild boars in Nagano Prefecture, Japan.

We investigated the prevalence of porcine circovirus 2 (PCV2) and 3 (PCV3) in wild boars captured or found dead in Nagano Prefecture in 2020. Based on PCR testing, 21 of 254 (8.3%) wild boars were PCV2-positive and 43 of 256 (16.8%) wild boars were PCV3-positive, 5 of 253 (2.0%) wild boars were both PCV2-positive and PCV3-positive. The frequency of detecting PCV3 in wild boars was significantly higher in adults than in juveniles (P=0.014). The PCV2-positive wild boars were found in all districts except for the North Alps and Hokushin, while PCV3-positive wild boars were found in all districts except for Suwa. This is the first report of PCV2 and PCV3 detected in wild boars in Japan.

Retrospective assessment of porcine circovirus 3 (PCV-3) in formalin-fixed, paraffin-embedded tissues from pigs affected by different clinical-pathological conditions.

BACKGROUND: Porcine circovirus 3 (PCV-3) is a recently discovered pathogen of swine that has been associated with several conditions. However, many questions remain unanswered regarding its infection, especially in terms of pathogenesis and disease impact. The aim of the present study was to retrospectively investigate the presence of PCV-3 genome by real time quantitative PCR (qPCR) and in situ hybridization (ISH) on selected formalin-fixed paraffin-embedded tissues of pigs affected by different clinical conditions and histological lesions. MATERIALS AND METHODS: Conditions investigated included porcine dermatitis and nephropathy syndrome (PDNS), periweaning failure-to-thrive syndrome (PFTS), congenital tremors type AII, reproductive disorders, and pigs affected by systemic periarteritis/arteritis, myocarditis, or encephalitis. Studied cases (n = 587) were investigated from a diagnostic database (n = 4162) that comprised samples collected within the period 1998-2021. From each condition/lesion, 10 to 12 cases were subsequently selected and tested by qPCR and ISH (72 cases total). RESULTS: A total of 587 cases fulfilled inclusion criteria of the different studied conditions and were distributed among the seven groups. For the further selected cases, PCV-3 genome was found by qPCR in 12/12 periarteritis, 5/10 reproductive disease, 5/10 PFTS, 3/10 myocarditis, 1/10 encephalitis and 1/10 congenital tremor cases. PCV-3 was not found in any of the PDNS cases assessed. In periarteritis cases, tissues more commonly affected were mesenteric arteries and kidney. Reproductive disease cases associated to PCV-3 genome consistently displayed myocarditis. The lesions and labelling distribution of PFTS cases with presence of PCV-3 genome were comparable to those of the periarteritis group. qPCR and ISH yielded similar results within each studied case and were statistically comparable. CONCLUSION: Our results suggest that periarteritis is the hallmark lesion of PCV-3-SD, and that mesenteric lymph node and kidney appeared to be the most reliable organs to confirm the presence of PCV-3 genome in cases with periarteritis.

Exploratory Study of the Frequency of Detection and Tissue Distribution of Porcine Circovirus 3 (PCV-3) in Pig Fetuses at Different Gestational Ages.

Porcine circovirus 3 (PCV-3) has been associated with several pig diseases. Despite the pathogenicity of this virus has not been completely clarified, reproductive disorders are consistently associated with its infection. The aim of the present work was to analyze the presence of PCV-3 DNA in tissues from pig fetuses from different gestational timepoints. The fetuses were obtained either from farms with no reproductive problems (NRP, n = 249; all of them from the last third of gestation) or from a slaughterhouse (S, n = 51; 49 of the second-third of gestation and 2 from the third one). Tissues collected included brain, heart, lung, kidney, and/or spleen. Overall, the frequency of detection of PCV-3 was significantly higher in fetuses from the last third of the gestation (69/251, 27.5%) when compared to those from the second-third (5/49, 10.2%), although the viral loads were not significantly different. Moreover, the frequency of detection in NRP fetuses (69/249, 27.7%) was significantly higher than in S ones (5/51, 9.8%). Furthermore, PCV-3 DNA was detected in all tissue types analyzed. In conclusion, the present study demonstrates a higher frequency of PCV-3 DNA detection in fetuses from late periods of the gestation and highlights wide organ distributions of the virus in pig fetuses.

Recent Progress on Epidemiology and Pathobiology of Porcine Circovirus 3.

The recently discovered porcine circovirus 3 (PCV3) belongs to the Circovirus genus of the Circoviridae family together with the other three PCVs, PCV1, PCV2, and PCV4. As reported, PCV3 can infect pig, wild boar, and several other intermediate hosts, resulting in single or multiple infections in the affected animal. The PCV3 infection can lead to respiratory diseases, digestive disorders, reproductive disorders, multisystemic inflammation, and immune responses. Up to now, PCV3 infection, as well as the disease caused by PCV3, has been reported in many swine farms worldwide with high positive rates, which indicates that the virus may be another important pathogen in the swine industry. Therefore, we reviewed the current progress on epidemiology and pathobiology of PCV3, which may provide the latest knowledge of the virus and PCV3-related diseases.

Porcine circovirus 3 (PCV-3) as a causal agent of disease in swine and a proposal of PCV-3 associated disease case definition.

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-3-reproductive 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 Detection in Aborted Fetuses and Stillborn Piglets from Swine Reproductive Failure Cases.

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.

Porcine circovirus 3 capsid protein induces autophagy in HEK293T cells by inhibiting phosphorylation of the mammalian target of rapamycin.

Porcine circovirus 3 (PCV3) has been detected in major pig-producing countries around the world since its first report in the US in 2016. Most current studies have focused on epidemiological investigations and detection methods of PCV3 because of lack of live virus strains for research on its pathogenesis in porcine cells or even in pigs. We constructed a recombinant plasmid pCMV-Cap carrying the PCV3 orf2 gene to investigate the effects of capsid (Cap) protein expression on autophagic response in human embryonic kidney cell line 293T (HEK293T). We demonstrate that PCV3 Cap protein induced complete autophagy shown as formation of autophagosomes and autophagosome-like vesicles as well as LC3-II conversion from LC3-I via inhibiting phosphorylation of the mammalian target of rapamycin (mTOR) in HEK293T cells. The ubiquitin-proteasome pathway is also involved in the autophagy process. These findings provide insight for further exploration of PCV3 pathogenetic mechanisms in porcine cells.

Porcine circoviruses: current status, knowledge gaps and challenges.

Circoviruses (CV) include some of the smallest viruses known. They were named after their circularly arranged single-stranded DNA genome with a gene encoding a conserved replicase protein on the sense strand. Circoviruses are widely distributed in mammals, fish, avian species and even insects. In pigs, four different CVs have been identified and named with consecutive numbers based on the order of their discovery: Porcine circovirus 1 (PCV1), Porcine circovirus 2 (PCV2), Porcine circovirus 3 (PCV3) and most recently Porcine circovirus 4 (PCV4). PCVs are ubiquitous in global pig populations and uninfected herds are rarely found. It is generally accepted that PCV1 is non-pathogenic. In contrast, PCV2 is considered an important, economically challenging pathogen on a global scale with comprehensive vaccination schemes in place. The role of PCV3 is still controversial several years after its discovery. Propagation of PCV3 appears to be challenging and only one successful experimental infection model has been published to date. Similarly to PCV2, PCV3 is widespread and found in many pigs regardless of their health history, including high health herds. PCV4 has only recently been discovered and further information on this virus is required to understand its potential impact. This review summarizes current knowledge on CVs in pigs and aims to contrast and compare known facts on PCVs.

Detection of Porcine Circovirus 3 in Wildlife Species in Spain.

Porcine circovirus 3 (PCV-3) is the third member of the family Circoviridae, genus Circovirus, able to infect swine. A high prevalence of viral DNA has been recorded in wild boars. Recently, PCV-3 DNA was identified in Italian wild ruminants. Based on these previous results, this study assessed the frequency of PCV-3 DNA detection in free-ranging ruminants and Lagomorpha species in Spain. In addition, the genetic characterization of the PCV-3 PCR-positive samples was performed. A total of 801 serum samples, including red deer (Cervus elaphus, [CE]; n = 108), roe deer (Capreolus capreolus, [CC]; n = 87), Pyrenean chamois (Rupicapra pyrenaica, [RP]; n = 133), Iberian ibex (Capra pyrenaica, [CP]; n = 92), mouflon (Ovis aries, [OA]; n = 91), fallow deer (Dama dama, [DD]; n = 104), European rabbit (Oryctolagus cuniculus, [OC]; n = 101), and European hare (Lepus europaeus, [LE]; n = 85) from Catalonia (northeast Spain) were tested by conventional polymerase chain reaction (PCR) and, when positive, sequenced. Overall, PCV-3 DNA was found in three out of 801 analyzed sera (0.37%) corresponding to one red deer (1/108, 0.9%), one mouflon (1/91, 1.1%), and one fallow deer (1/104, 0.96%). None of the samples collected from Lagomorpha species resulted PCR positive. The partial genome sequences detected in positive samples displayed high identity with some PCV-3 sequences detected in wild boars and domestic pigs (99.7% and 100%, respectively). In conclusion, the present study indicated that free-ranging ruminant and Lagomorpha species are not relevant in the epidemiology of PCV-3 in Spain.

Similar frequency of Porcine circovirus 3 (PCV-3) detection in serum samples of pigs affected by digestive or respiratory disorders and age-matched clinically healthy pigs.

Porcine circovirus 3 (PCV-3) has been identified in pigs affected by different disease conditions, although its pathogenicity remains unclear. The objective of the present study was to assess the frequency of PCV-3 infection in serum samples from animals suffering from post-weaning respiratory or digestive disorders as well as in healthy animals. A total of 315 swine serum samples were analysed for PCV-3 DNA detection by conventional PCR; positive samples were further assayed with a quantitative PCR and partially sequenced. Sera were obtained from 4 week- to 4 month-old pigs clinically diagnosed with respiratory (n = 129) or digestive (n = 126) disorders. Serum samples of age-matched healthy animals (n = 60) served as negative control. Pigs with clinical respiratory signs had a wide variety of pulmonary lesions including suppurative bronchopneumonia, interstitial pneumonia, fibrinous-necrotizing pneumonia and/or pleuritis. Animals with enteric signs displayed histopathological findings like villus atrophy and fusion, catarrhal enteritis and/or catarrhal colitis. Overall, PCV-3 DNA was detected in 19 out of 315 analysed samples (6.0%). Among the diseased animals, PCV-3 was found in 6.2% (8 out of 129) and 5.6% (7 out of 126) of pigs with respiratory and digestive disorders, respectively. The frequency of PCV-3 PCR positive samples among healthy pigs was 6.7% (4 out of 60). No apparent association was observed between PCR positive cases and any type of histopathological lesion. The phylogenetic analysis of the partial genome sequences obtained showed high identity among viruses from the three groups of animals studied. In conclusion, PCV-3 was present in the serum of diseased and healthy pigs to similar percentages, suggesting that this virus does not seem to be causally associated with respiratory or enteric disorders.

ITRAQ-based quantitative proteomics reveals the first proteome profiles of piglets infected with porcine circovirus type 3.

Porcine circovirus type 3 (PCV3) infection induces porcine dermatitis and nephropathy syndrome, reproductive failure, and multisystemic inflammatory lesions in piglets and sows. To better understand the host responses to PCV3 infection, isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with LC-MS/MS analysis was used for quantitative determination of differentially regulated cellular proteins in the lungs of specific-pathogen-free piglets after 4 weeks of PCV3 infection. Totally, 3429 proteins were detected in three independent mass spectrometry analyses, of which 242 differential cellular proteins were significantly regulated, consisting of 100 upregulated proteins and 142 downregulated proteins in PCV3-infected group relative to control group. Bioinformatics analysis revealed that these higher or lower abundant proteins involved primarily metabolic processes, innate immune response, MHC-I and MHC-II components, and phagosome pathways. Ten genes encoding differentially regulated proteins were selected for investigation via real-time RT-PCR. The expression levels of six representative proteins, OAS1, Mx1, ISG15, IFIT3, SOD2, and HSP60, were further confirmed by Western blotting and immunohistochemistry. This study attempted for the first time to investigate the protein profile of PCV3-infected piglets using iTRAQ technology; our findings provide valuable information to better understand the mechanisms underlying the host responses to PCV3 infection in piglets. SIGNIFICANCE: Our study identified differentially abundant proteins related to a variety of potential signaling pathways in the lungs of PCV3-infected piglets. These findings provide valuable information to better understand the mechanisms of host responses to PCV3 infection.

Porcine circovirus 3 capsid protein induces autophagy in HEK293T cells by inhibiting phosphorylation of the mammalian target of rapamycin / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Porcine circovirus 3 (PCV3) has been detected in major pig-producing countries around the world since its first report in the US in 2016. Most current studies have focused on epidemiological investigations and detection methods of PCV3 because of lack of live virus strains for research on its pathogenesis in porcine cells or even in pigs. We constructed a recombinant plasmid pCMV-Cap carrying the PCV3 orf2 gene to investigate the effects of capsid (Cap) protein expression on autophagic response in human embryonic kidney cell line 293T (HEK293T). We demonstrate that PCV3 Cap protein induced complete autophagy shown as formation of autophagosomes and autophagosome-like vesicles as well as LC3-II conversion from LC3-I via inhibiting phosphorylation of the mammalian target of rapamycin (mTOR) in HEK293T cells. The ubiquitin-proteasome pathway is also involved in the autophagy process. These findings provide insight for further exploration of PCV3 pathogenetic mechanisms in porcine cells.

Porcine circovirus 3 capsid protein induces autophagy in HEK293T cells by inhibiting phosphorylation of the mammalian target of rapamycin / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Porcine circovirus 3 (PCV3) has been detected in major pig-producing countries around the world since its first report in the US in 2016. Most current studies have focused on epidemiological investigations and detection methods of PCV3 because of lack of live virus strains for research on its pathogenesis in porcine cells or even in pigs. We constructed a recombinant plasmid pCMV-Cap carrying the PCV3 orf2 gene to investigate the effects of capsid (Cap) protein expression on autophagic response in human embryonic kidney cell line 293T (HEK293T). We demonstrate that PCV3 Cap protein induced complete autophagy shown as formation of autophagosomes and autophagosome-like vesicles as well as LC3-II conversion from LC3-I via inhibiting phosphorylation of the mammalian target of rapamycin (mTOR) in HEK293T cells. The ubiquitin-proteasome pathway is also involved in the autophagy process. These findings provide insight for further exploration of PCV3 pathogenetic mechanisms in porcine cells.

A Shift in Porcine Circovirus 3 (PCV-3) History Paradigm: Phylodynamic Analyses Reveal an Ancient Origin and Prolonged Undetected Circulation in the Worldwide Swine Population.

The identification of a new circovirus (Porcine circovirus 3, PCV-3) has raised a remarkable concern because of some analogies with Porcine circovirus 2 (PCV-2). Preliminary results suggest an extremely recent PCV-3 emergence and high mutation rate. Retrospective studies prove its circulation at least since the early 1990s, revealing that PCV-3 could have been infecting pigs for an even longer period. Therefore, a new evaluation, based on an updated collection of PCV-3 sequences spanning more than 20 years, is performed using a phylodynamic approach. The obtained results overrule the previous PCV-3 history concept, indicating an ancient origin. These evidences are associated with an evolutionary rate far lower (10-5-10-6 substitution/site/year) than the PCV-2 one. Accordingly, the action of selective pressures on PCV-3 open reading frames (ORFs) seems to be remarkably lower compared to those acting on PCV-2, suggesting either a reduced PCV-3 plasticity or a less efficient host-induced natural selection. A complex and not-directional viral flow network is evidenced through phylogeographic analysis, indicating a long lasting circulation rather than a recent emergence followed by spreading. Being recent emergence has been ruled out, efforts should be devoted to understand whether its recent discovery is simply due to improved detection capabilities or to the breaking of a previous equilibrium.

Transmission of Porcine Circovirus 3 (PCV3) by Xenotransplantation of Pig Hearts into Baboons.

Porcine circovirus 3 (PCV3) is a newly described member of the virus family Circoviridae. PCV3 is highly distributed among pigs and wild boars worldwide. A sudden introduction of PCV3 was recently observed in a herd of triple genetically modified pigs generated for xenotransplantation. These animals were used as donor pigs for orthotopic heart transplantation into baboons. In four cases, PCV3-positive hearts were transplanted, and transmission of PCV3 to the recipient was observed. PCV3 was found in all organs of the recipient baboons and a higher virus load was found in animals with a longer survival time of the transplant, indicating replication of the virus. This is the first report showing trans-species transmission of PCV3 to baboons by transplantation of a heart from a PCV3-positive donor pig. Sequence analysis showed that PCV3a and PCV3b were present in the infected pigs and were transmitted. Experiments to infect human 293 cells with PCV3 failed.

Recent progress on porcine circovirus type 3.

Porcine circovirus 3 (PCV3) is a newly identified virus that belongs to the genus Circovirus in the family Circoviridae. Since the first identification of PCV3 in domestic swine in 2016 in the USA, exciting progress on PCV3 has emphasized the importance of the virus. The aim of this review is to present recent advances in the molecular characteristics, epidemiology, and pathogenesis of PCV3. The virus spreads widely throughout almost all tissues of pig and wild boar in various countries, with a gradual increase of the infection. PCV3 is a pathogen associated with porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs, reproductive failure, and cardiac and multiorgan inflammation. Furthermore, PCV3 has been detected in other animals and ticks, suggesting that PCV3 possesses cross-species transmission abilities and has an unexpectedly broad distribution and circulation in the wild, where these animals may serve as potential reservoirs for PCV3 and pose a threat to the swine industry or even to humans. Moreover, several detection methods, which can specifically detect PCV3 or differentiate PCV3 from the other viruses, are also reviewed. The present review provides updated knowledge on PCV3-related research. Identification of the prevailing strain of PCV3 and its reservoirs is essential for researchers to understand PCV3 infections and PCV3-related diseases.