Porcine circovirus type 2-associated disease: Update on current terminology, clinical manifestations, pathogenesis, diagnosis, and intervention strategies

doi:10.1177/104063870701900601

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Porcine circovirus type 2-associated disease: Update on current terminology, clinical manifestations, pathogenesis, diagnosis, and intervention strategies

Journal Article•DOI•

Porcine circovirus type 2-associated disease: Update on current terminology, clinical manifestations, pathogenesis, diagnosis, and intervention strategies

Tanja Opriessnig¹, Xiang-Jin Meng², Patrick G. Halbur¹•Institutions (2)

Iowa State University¹, Virginia Tech²

01 Nov 2007-Journal of Veterinary Diagnostic Investigation (SAGE Publications)-Vol. 19, Iss: 6, pp 591-615

TL;DR: The most common disease manifestations, pathogenesis, diagnostic approaches, and intervention strategies associated with PCVAD in North America are discussed.

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Abstract: Porcine circovirus type 2 (PCV2)-associated disease (PCVAD) continues to be an important differential diagnosis on pig farms in the United States and worldwide. Case trend analyses indicate that the incidence of PCVAD is on the rise in the United States. Accurate diagnosis is important in order to implement appropriate intervention strategies. PCVAD can manifest as a systemic disease, as part of the respiratory disease complex, as an enteric disease, as porcine dermatitis and nephropathy syndrome, or as reproductive problems. PCVAD may be only a sporadic individual animal diagnosis; however, PCVAD may also manifest as a severe herd problem accelerated and enhanced by concurrent virus or bacterial infections. This article is intended to discuss the most common disease manifestations, pathogenesis, diagnostic approaches, and intervention strategies associated with PCVAD in North America.

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Journal Article•DOI•

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

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Joaquim Segalés¹•Institutions (1)

Autonomous University of Barcelona¹

01 Mar 2012-Virus Research

TL;DR: 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, and a proposal on a unified PCVD/PCVAD terminology and clearly defined diagnostic criteria for these conditions are given.

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450 citations

Journal Article•DOI•

Multiple Diverse Circoviruses Infect Farm Animals and Are Commonly Found in Human and Chimpanzee Feces

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Linlin Li¹, Amit Kapoor¹, Amit Kapoor², Beth Slikas², Beth Slikas¹, Oderinde Soji Bamidele³, Chunlin Wang⁴, S. Shahid Shaukat, Muhammad Alam Masroor, Michael L. Wilson⁵, Jean Bosco N. Ndjango⁶, Martine Peeters⁷, Nicole Gross-Camp⁸, Martin N. Muller⁹, Beatrice H. Hahn¹⁰, Nathan D. Wolfe¹¹, Nathan D. Wolfe⁴, Hinda Triki¹², Joanne M. Bartkus, Syed Sohail Zahoor Zaidi, Eric Delwart², Eric Delwart¹ - Show less +18 more•Institutions (12)

Systems Research Institute¹, University of California, San Francisco², University of Maiduguri³, Stanford University⁴, University of Minnesota⁵, University of Kisangani⁶, Institut de recherche pour le développement⁷, University of East Anglia⁸, University of New Mexico⁹, University of Alabama at Birmingham¹⁰, Global Viral¹¹, Pasteur Institute¹²

15 Feb 2010-Journal of Virology

TL;DR: It is shown that the genetic diversity of small circular DNA viral genomes in various mammals, including humans, is significantly larger than previously recognized, and frequent exposure through meat consumption and contact with animal or human feces provides ample opportunities for cyclovirus transmission.

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Abstract: Circoviruses are known to infect birds and pigs and can cause a wide range of severe symptoms with significant economic impact. Using viral metagenomics, we identified circovirus-like DNA sequences and characterized 15 circular viral DNA genomes in stool samples from humans in Pakistan, Nigeria, Tunisia, and the United States and from wild chimpanzees. Distinct genomic features and phylogenetic analysis indicate that some viral genomes were part of a previously unrecognized genus in the Circoviridae family we tentatively named “Cyclovirus” whose genetic diversity is comparable to that of all the known species in the Circovirus genus. Circoviridae detection in the stools of U.S. adults was limited to porcine circoviruses which were also found in most U.S. pork products. To determine whether the divergent cycloviruses found in non-U.S. human stools were of dietary origin, we genetically compared them to the cycloviruses in muscle tissue samples of commonly eaten farm animals in Pakistan and Nigeria. Limited genetic overlap between cycloviruses in human stool samples and local cow, goat, sheep, camel, and chicken meat samples indicated that the majority of the 25 Cyclovirus species identified might be human viruses. We show that the genetic diversity of small circular DNA viral genomes in various mammals, including humans, is significantly larger than previously recognized, and frequent exposure through meat consumption and contact with animal or human feces provides ample opportunities for cyclovirus transmission. Determining the role of cycloviruses, found in 7 to 17% of non-U.S. human stools and 3 to 55% of non-U.S. meat samples tested, in both human and animal diseases is now facilitated by knowledge of their genomes.

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352 citations

Cites background from "Porcine circovirus type 2-associate..."

...ciated diseases, which can manifest as a systemic disease, respiratory disease complex, enteric disease, porcine dermatitis and nephropathy syndrome or as reproductive problems, causing great losses in the pork industry (1, 29, 32)....
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Journal Article•DOI•

Polymicrobial respiratory disease in pigs

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Tanja Opriessnig¹, Luis G. Giménez-Lirola¹, Patrick G. Halbur¹•Institutions (1)

Iowa State University¹

01 Dec 2011-Animal Health Research Reviews

TL;DR: This review discusses the latest findings on polymicrobial respiratory disease in pigs and recommends best practices for control of swine respiratory disease outbreaks caused by concurrent infection of two or more pathogens.

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Abstract: Respiratory disease in pigs is common in modern pork production worldwide and is often referred to as porcine respiratory disease complex (PRDC). PRDC is polymicrobial in nature, and results from infection with various combinations of primary and secondary respiratory pathogens. As a true multifactorial disease, environmental conditions, population size, management strategies and pig-specific factors such as age and genetics also play critical roles in the outcome of PRDC. While non-infectious factors are important in the initiation and outcome of cases of PRDC, the focus of this review is on infectious factors only. There are a variety of viral and bacterial pathogens commonly associated with PRDC including porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), porcine circovirus type 2 (PCV2), Mycoplasma hyopneumoniae (MHYO) and Pasteurella multocida (PMULT). The pathogenesis of viral respiratory disease is typically associated with destruction of the mucocilliary apparatus and with interference and decrease of the function of pulmonary alveolar and intravascular macrophages. Bacterial pathogens often contribute to PRDC by activation of inflammation via enhanced cytokine responses. With recent advancements in pathogen detection methods, the importance of polymicrobial disease has become more evident, and identification of interactions of pathogens and their mechanisms of disease potentiation has become a topic of great interest. For example, combined infection of pigs with typically low pathogenic organisms like PCV2 and MHYO results in severe respiratory disease. Although the body of knowledge has advanced substantially in the last 15 years, much more needs to be learned about the pathogenesis and best practices for control of swine respiratory disease outbreaks caused by concurrent infection of two or more pathogens. This review discusses the latest findings on polymicrobial respiratory disease in pigs.

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301 citations

Cites background from "Porcine circovirus type 2-associate..."

...Until there was widespread implementation of vaccine protocols, the different disease manifestations of PCV2 in pigs including respiratory disease were associated with high morbidity and mortality rates in pigs (Opriessnig et al., 2007)....
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Porcine circovirus type 2 (PCV2) infections: Clinical signs, pathology and laboratory diagnosis

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oaquim Segalésa

01 Jan 2012

TL;DR: In this article, a review of the current knowledge on the clinical and pathological scope of PCV2 infections, as well as on their diagnosis is presented, and a unified PCVD/PCVAD terminology and clearly defined diagnostic criteria for these conditions are also given.

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Abstract: 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.

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276 citations

Journal Article•DOI•

Porcine Circovirus Type 2 and Porcine Circovirus-Associated Disease

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J. Gillespie¹, Tanja Opriessnig¹, Xiang-Jin Meng¹, K. Pelzer¹, Virginia Buechner-Maxwell¹ - Show less +1 more•Institutions (1)

Virginia–Maryland Regional College of Veterinary Medicine¹

01 Nov 2009-Journal of Veterinary Internal Medicine

TL;DR: An overview of current knowledge relating to PCV2 and PCVAD with an emphasis on information relevant to the swine veterinarian is provided.

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Abstract: Porcine circovirus type 2 (PCV2) belongs to the viral family Circoviridae and to the genus Circovirus. Circoviruses are small, single-stranded nonenveloped DNA viruses that have an unsegmented circular genome. PCV2 is the primary causative agent of several syndromes collectively known as porcine circovirus-associated disease (PCVAD). Many of the syndromes associated with PCVAD are a result of coinfection with PCV2 virus and other agents such as Mycoplasma and porcine reproductive and respiratory syndrome virus. PCV2 infection is present in every major swine-producing country in the world, and the number of identified cases of PCVAD is rapidly increasing. In the United States, the disease has cost producers an average of 3-4 dollars per pig with peak losses ranging up to 20 dollars per pig. The importance of this disease has stimulated investigations aimed at identifying risk factors associated with infection and minimizing these risks through modified management practices and development of vaccination strategies. This paper provides an overview of current knowledge relating to PCV2 and PCVAD with an emphasis on information relevant to the swine veterinarian.

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249 citations

Cites background from "Porcine circovirus type 2-associate..."

...There are 4 main factors essential in the expression of PCV2-related diseases: viral effects, host effects, and the effects of coinfection and immunomodulation.(23)...
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...Detection of PCV2 antigen or nucleic acid is considered the gold standard for the diagnosis of PCVAD....
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...Granulomatous lesions can also be found in the lungs, liver, kidney, heart, and intestines.(23) A scoring system has been developed that estimates the severity of disease based on the extent of lymphatic tissue involvement....
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...If only limited PCV2 antigen is found but there are severe lesions, it is classified as chronic severe PCVAD.(23) Scoring of lesions and the amount of antigen in tissues allows for staging of infection....
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...The significance of this finding to the pig is unknown, but can cause the carcass to be condemned at slaughter.(23)...
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References

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Open Access

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Virus taxonomy : eighth report of the International Committee on Taxonomy of Viruses

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Claude M. Fauquet, Mayo, J. Maniloff, U. Desselberger, L. A. Ball - Show less +1 more

01 Jan 2005

4,979 citations

Journal Article•DOI•

Porcine circoviruses: a review.

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Gordon Allan, John A. Ellis¹•Institutions (1)

Western University College of Veterinary Medicine¹

01 Jan 2000-Journal of Veterinary Diagnostic Investigation

TL;DR: The diagnosis of PCV2-associated disease is based on the direct demonstration ofPCV2 antigens or nucleic acid in affected tissues, as is the role of the immune response in controlling or augmenting disease.

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Abstract: Porcine circoviruses (PCV) are small nonenveloped DNA viruses containing a unique single-stranded circular genome. Previously, no recognized link was found between PCV infection of pigs and disease, and PCV was considered a nonpathogenic agent. Over the last 5 years, a "novel" PCV, designated PCV2, has been associated with various disease syndromes in pigs, primarily postweaning multisystemic wasting syndrome (PMWS). Pigs with PMWS have a variety of clinical signs, including debility, dyspnea, palpable lymphadenopathy, diarrhea, and pallor or icterus. Lesions associated with the presence of PCV2 in a variety of cell types include lymphohistiocytic to granulomatous interstitial pneumonia, hepatitis, nephritis, myocarditis, enteritis, and pancreatitis. The lesions of PMWS have been reproduced experimentally after inoculation of piglets with PCV2 cell culture isolates, although the full expression of the disease syndrome may require the presence of other agents such as porcine parvovirus or porcine reproductive and respiratory syndrome (PRRS) virus. Recent reports have linked PCV2 to other disorders in pigs, ranging from abortion and reproductive failure to "atypical" PRRS. Available data indicate high seroprevalence of antibodies to PCV2 worldwide. The diagnosis of PCV2-associated disease is based on the direct demonstration of PCV2 antigens or nucleic acid in affected tissues. PCV2 is now regarded as an important emerging pathogen. Although vertical transmission has been documented, the epidemiology of PCV2 infections is poorly understood, as is the role of the immune response in controlling or augmenting disease.

...read moreread less

785 citations

"Porcine circovirus type 2-associate..." refers background in this paper

...PCV2 can be found in healthy pigs as well as in diseased pigs.(3) This makes the choice and interpretation of diagnostic tests important for confirmation of PCVAD....
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...Immunohistochemistry (IHC) or ISH techniques demonstrate large amounts of PCV2 antigen or nucleic acids in the cytoplasm of macrophages and dendritic cells replacing lymphocytes in the depleted follicles in lymphoid tissues.(3,20,128) However, PCV2 antigen in lymphocytes was only sporadically detected,(20) and it is still unknown whether the reduction of lymphocytes in PCVAD-affected pigs is due to reduced production in the bone marrow, reduced proliferation in secondary lymphoid tissues, or increased loss of lymphocytes in the bone marrow, peripheral blood, or secondary lymphoid tissues via virus-induced necrosis or apoptosis....
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Journal Article•DOI•

A very small porcine virus with circular single-stranded DNA

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I. Tischer¹, Hans R. Gelderblom¹, W. Vettermann¹, M. A. Koch¹•Institutions (1)

Robert Koch Institute¹

07 Jan 1982-Nature

TL;DR: During the search for an in vitro model of persistent virus infections the agent was studied in more detail and showed the virus to have a diameter of 17 nm, and to contain a covalently closed circular single-stranded DNA with a molecular weight of 0.58 × 106.

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Abstract: It was reported previously that cultures of the porcine PK-15 cell line (ATCC-CCL31) were chronically infected with a small virus, supposedly containing RNA1. No gross cytopathic effect was seen in these cultures. During the search for an in vitro model of persistent virus infections the agent was studied in more detail. These studies showed the virus to have a diameter of 17 nm, and to contain a covalently closed circular single-stranded DNA with a molecular weight of 0.58 × 106 and a main capsid polypeptide with a molecular weight of 36,000. Of the animals tested, only pigs were found to have antibodies. On the basis of these properties the virus appears to be a member of a family of animal viruses so far not encountered. We have named the virus porcine circovirus (PCV).

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680 citations

Journal Article•DOI•

Isolation of Porcine Circovirus-like Viruses from Pigs with a Wasting Disease in the USA and Europe:

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Gordon Allan, F. McNeilly, S. Kennedy, B. M. Daft¹, E. G. Clarke², John Ellis², Deborah M. Haines², Brian M. Meehan, B. M. Adair - Show less +5 more•Institutions (2)

University of California, Davis¹, Western University College of Veterinary Medicine²

01 Jan 1998-Journal of Veterinary Diagnostic Investigation

TL;DR: Although genomic analysis for the definitive identification of these viral isolates remains to be done, the evidence provided strongly suggests that these tissue isolates are closely related to, although antigenically distinct from, the original PCV cell culture contaminant.

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Abstract: Samples of lung, liver, kidney, pancreas, spleen, and lymph node from pigs with postweaning multisystemic wasting syndrome from California (USA) and samples of mesenteric lymph nodes from similarly diseased pigs from Brittany (France) were examined by light microscopy, in situ hybridization (ISH), and/or virus isolation. Whole genomic probes for porcine circovirus (PCV) and chicken anemia virus (CAV) were used for ISH. Tissue homogenate supernatants were inoculated onto PK/15 cells for virus isolation, and the presence of viral antigen and viral particles was verified by indirect immunofluorescence, ISH, and electron microscopy. Histologic examination of lung from pigs from California revealed interstitial pneumonia, alveolar epithelial hyperplasia, and basophilic nuclear and cytoplasmic inclusions in mononuclear cell infiltrates and various pulmonary epithelial cells. Granulomatous lymphadenitis with syncytial cells typified the lesions seen in the pigs from France. PCV-like nucleic acid was detected by ISH in lung, pancreas, lymph node, kidney, and liver in pigs from California. Positive signal was also obtained in lymph node sections from pigs from France. Probes for CAV were consistently negative. PK/15 cell cultures inoculated with lung preparations from diseased California pigs and mesenteric lymph node preparations from pigs from France had positive fluores- cence by indirect staining for PCV using pooled polyclonal pig sera and hyperimmune rabbit serum and had variable staining with a panel of 7 monoclonal antibodies specific for cell culture contaminant PCV. PCV-like nucleic acid was also detected by ISH in cell cultures. Cytopathic effect was not observed. Electron microscopic examination of inoculated cell cultures revealed 17-nm viral particles morphologically consistent with PCV. No other virus particles were observed. Although genomic analysis for the definitive identification of these viral isolates remains to be done, the evidence provided strongly suggests that these tissue isolates are closely related to, although antigenically distinct from, the original PCV cell culture contaminant. Porcine circovirus (PCV) was first detected as a contaminant of a continuous pig kidney cell line (PK/ 15). 17 Since this initial identification, this virus has been shown to contain a single-stranded circular DNA genome of 1.76 kb 13,15 and is now classified in a new virus family, the Circoviridae. 11 Serum antibody to PCV has been demonstrated in pigs from Germany, 15,16 Canada, 7 New Zealand, 10 Great Britain, 8 and Northern Ireland. 4 Experimental infections of pigs with PCV in- ocula, derived from contaminated PK/15 cell cultures, have failed to produce clinical disease. 3,16 Although several PCV isolates have been recovered from still- born piglets in Northern Ireland, 3 the potential of these

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536 citations

"Porcine circovirus type 2-associate..." refers background or methods in this paper

...Indirect fluorescent antibody (IFA) assays for PCV2 have been described in the literature.(7,111,132) Recently, an IFA assay based on an open reading frame (ORF) 2 protein has been described,(113) and it was found that the regular whole PCV2-based IFA assay had only a 57....
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...In the late 1990s, a variant strain of PCV was associated with a newly emerged disease syndrome in pigs, which became known as postweaning multisystemic wasting syndrome (PMWS).(7) Sequence analyses of the PMWS-associated PCV revealed significant genetic differences compared with the PK-15 cell-derived PCV....
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...Studies have shown that there is a low level of cross-reactivity between PCV1 and PCV2 on the IFA test.(7,111)...
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Journal Article•DOI•

Porcine circovirus diseases.

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Joaquim Segalés, Gordon Allan, Mariano Domingo¹•Institutions (1)

Autonomous University of Barcelona¹

01 Dec 2005-Animal Health Research Reviews

TL;DR: The objective of this review is to summarize the current state of knowledge of the most relevant aspects of PCV2 biology and PCVD.

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Abstract: Porcine circovirus type 2 (PCV2) is a member of the family Circoviridae, a recently established virus family composed of small, non-enveloped viruses, with a circular, single-stranded DNA genome. PCV2, which is found all over the world in the domestic pig and probably the wild boar, has been recently associated with a number of disease syndromes, which have been collectively named porcine circovirus diseases (PCVD). Postweaning multisystemic wasting syndrome (PMWS), porcine dermatitis and nephropathy syndrome (PDNS) and reproductive disorders are the most relevant ones. Among them, only PMWS is considered to have a severe impact on domestic swine production. PMWS mainly affects nursery and/or fattening pigs; wasting is considered the most representative clinical sign in this disease. Diagnosis of this disease is confirmed by histopathological examination of lymphoid tissues and detection of a moderate to high amount of PCV2 in damaged tissues. Since PMWS is considered a multifactorial disease in which other factors in addition to PCV2 are needed in most cases to trigger the clinical disease, effective control measures have focused on the understanding of the co-factors involved in individual farms and the control or elimination of these triggers. PDNS, an immuno-complex disease characterized by fibrino-necrotizing glomerulonephritis and systemic necrotizing vasculitis, has been linked to PCV2, but a definitive proof of this association is still lacking. PCV2-associated reproductive disease seems to occur very sporadically under field conditions, but it has been characterized by late-term abortions and stillbirths, extensive fibrosing and/or necrotizing myocarditis in fetuses and the presence of moderate to high amounts of PCV2 in these lesions. Taking into account that scientific information on PCV2 and its associated diseases has been markedly expanded in the last 8 years, the objective of this review is to summarize the current state of knowledge of the most relevant aspects of PCV2 biology and PCVD.

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534 citations

"Porcine circovirus type 2-associate..." refers methods in this paper

...Seven-month-old boars were inoculated intranasally with PCV2....
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...Serological studies have found that PCV2 antibodies are present globally in almost all swine herds tested and in up to 100% of individual pigs within herds.83,108,139 Most US breeding herds and most of the sows within those herds were found to be seropositive for PCV2....
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...To increase the ability to detect very small amounts of the target sequence, nested PCR assays have been described.57,60,75 3) Multiplex-nested PCR assays have been described for the simultaneous detection of PCV1/PCV2/PPV58,66 and PCV1/PCV2....
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...591 from a 2000 porcine dermatitis and nephropathy syndrome (PDNS) case, implying that a similar PCV2 isolate has been present in the UK pig population for more than 30 years.40 Archived tissues from 189 pigs and archived sera from 388 pigs collected from 1985 to 1997 in Spain were tested for the presence of PCV2 DNA by in situ hybridization (ISH) and for the presence of PCV2specific antibodies by IPMA.115 Approximately 41.3% (78/189) of the tissues were found to be ISH positive for PCV2, and 72.7% (282/388) of the sera were found to be IPMA positive, which is indicative of enzootic infection in Spain since 1985.115 PCV2 antibodies were detected in most pig serum samples collected in Northern Ireland from 1973 to 1999.139 The percentage of PCV2-seropositive sera showed an increased incidence in the samples collected in 1988 (100%; 80/80) and 1999 (92.1%; 129/140) when compared with 1973 (69.1%; 56/80), 1981 (61.3%; 49/80), and 1984 (55%; 44/80).139 Archived serum samples obtained from Canadian slaughterhouses were tested by indirect fluorescent assay (IFA) for antibodies to PCV1 and PCV2....
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...16 Mild interstitial pneumonia and lymphoplasmacytic rhinitis was induced in conventional pigs inoculated with PCV2....
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