Genetic and experimental comparison of porcine circovirus type 2 (PCV2) isolates from cases with and without PCV2-associated lesions provides evidence for differences in virulence

Opriessnig, Tanja; McKeown, N. E.; Zhou, En‐Min; Meng, Xiang‐Jin; Halbur, Patrick G.

doi:10.1099/vir.0.82099-0

Cited by 86 publications

(71 citation statements)

References 46 publications

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“…While differences in virulence between PCV2 isolates exist (Opriessnig et al, 2006), this appears not to be confined to genotype (Opriessnig et al, 2008). To our knowledge, this is the first study comparing apoptosis in pigs infected with PCV2a or PCV2b.…”

Section: Discussionmentioning

confidence: 95%

“…This is in contrast to the outcomes obtained in the current study and may be due to the fact that lower numbers of pigs were used in the previous study (Krakowka et al, 2004) as well as different challenge virus and different tissues were evaluated. In addition, virus dependent factors such as PCV2 isolates can be closely related and yet be exclusive, differences in detection systems for apoptosis and PCV2 may influence results, and host-dependent factors such as host susceptibility and immune response have been shown to be important (Opriessnig et al, 2006(Opriessnig et al, , 2007(Opriessnig et al, , 2009.…”

Section: Discussionmentioning

confidence: 99%

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Singular PCV2a or PCV2b infection results in apoptosis of hepatocytes in clinically affected gnotobiotic pigs

Sinha

Schalk

Lager

et al. 2012

Research in Veterinary Science

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Porcine circovirus type 2 (PCV2) is clinically associated with respiratory disease, failure-to-thrive, hepatitis, and diarrhea; however, the precise pathogenesis of PCV2-associated disease and in particular its involvement in apoptosis is still controversial. The objectives of this study were (1) to determine whether PCV2 is associated with apoptosis by examining and comparing hepatic tissues from clinically affected or unaffected gnotobiotic pigs that were experimentally infected with PCV2, (2) to determine if there are differences between PCV2a and PCV2b in inducing hepatocyte apoptosis, and (3) to determine if there are differences between apoptosis detection systems. Forty-eight gnotobiotic pigs were separated into five groups based on inoculation status and development of clinical disease: (1) sham-inoculated, clinically-unaffected (n = 4), (2) inoculated with PCV2a, clinically-unaffected (n = 10), (3) inoculated with PCV2a, clinically-affected (n = 6), (4) inoculated with PCV2b, clinically-unaffected, (n = 13) and (5) inoculated with PCV2b, clinically-affected (n = 15). Formalin-fixed, paraffin-embedded sections of liver from all pigs were analyzed for signs of apoptosis [presence of single strand DNA breaks in the nucleus by the terminal transferase dUTP nick end labeling (TUNEL) assay or presence of intra-nuclear cleaved caspase 3 (CCasp3) demonstrated by CCasp3 immunohistochemistry (IHC)]. In addition, the liver tissues were also tested for presence of cytoplasmic and intra-nuclear PCV2 antigen by an IHC assay. Specific CCasp3 and TUNEL labeling was detected in the nucleus of hepatocytes in PCV2a and PCV2b infected pigs with significantly (P < 0.05) higher levels of apoptotic cells in clinically-affected pigs. Regardless of PCV2 subtype (PCV2a; PCV2b), there were higher levels of PCV2 antigen in clinically-affected pigs compared to clinically-unaffected pigs. There was no significant difference in detection rate of apoptotic cells between the TUNEL assay and CCasp3 IHC. When high amounts of PCV2 antigen were present, the incidence of CCasp3 and TUNEL staining also increased regardless of the PCV2 genotype. This suggests that PCV2-induced apoptosis of hepatocytes is important in the pathogenesis of PCV2-associated lesions and disease. RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. b s t r a c tPorcine circovirus type 2 (PCV2) is clinically associated with respiratory disease, failure-to-thrive, hepatitis, and diarrhea; however, the precise pathogenesis of PCV2-associated disease and in particular its involvement in apoptosis is still controversial. The objectives of this study were (1) to determine whether PCV2 is associated with apoptosis by examining and comparing hepatic tissues from clinically affected or unaffected gnotobiotic pigs that were experimentally infected with PCV2, (2) to determine if there are differences between PCV2a and PCV2b in inducing hepatocyte ...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Singular PCV2a or PCV2b infection results in apoptosis of hepatocytes in clinically affected gnotobiotic pigs

Sinha

Schalk

Lager

et al. 2012

Research in Veterinary Science

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“…DQ397521) was recovered from a subclinically infected pig on an Iowa farm in 2003 and is of low virulence, based on experimental inoculations (Opriessnig et al, 2006c).…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, nearly identical PCV2 genomes have been found in healthy pigs and in diseased pigs from affected and unaffected herds (de Boisseson et al, 2004;Larochelle et al, 2002). In contrast, a PCV2a field isolate from a case with moderate-to-severe PCV2-associated lesions was compared with a PCV2a isolate from a case with no PCV2-associated lesions and significant differences in expression of lesions were seen in experimentally inoculated pigs (Opriessnig et al, 2006c). To our knowledge, with the exception of one small study done in germ-free pigs (Lager et al, 2007) and one study using conventional PCV2-seropositive pigs (Fort et al, 2008), a thorough head-to-head comparison of the virulence of PCV2a and PCV2b isolates has not yet been done.…”

Section: Introductionmentioning

confidence: 99%

Differences in virulence among porcine circovirus type 2 isolates are unrelated to cluster type 2a or 2b and prior infection provides heterologous protection

Opriessnig

Ramamoorthy

Madson

et al. 2008

Journal of General Virology

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116

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Porcine circovirus type 2 (PCV2) is divided into two genetic clusters designated PCV2a and PCV2b. The objectives of this study were to determine whether isolates from different clusters vary in virulence and to determine whether infection with PCV2a isolates induces protective immunity against subsequent infection with a recent PCV2b isolate. One-hundred and thirteen conventional specific-pathogen-free (SPF) pigs were assigned randomly to treatment groups and rooms: pigs inoculated with PCV2a cluster isolates (ISU-40895 or ISU-4838), pigs inoculated with PCV2b cluster isolates (NC-16845 or Can-17639) and uninoculated pigs. Necropsies were performed at 16 or 51 days post-inoculation (p.i.). There were no significant differences in PCV2-associated lymphoid lesions between PCV2a and PCV2b clusters; however, within the same cluster, significant differences were found between isolates: ISU-4838-and Can-17639-inoculated pigs had significantly (P,0.05) less severe lesions compared with ISU-40895-and NC-16845-inoculated pigs. To evaluate cross-protection, six pigs within each group were challenged at 35 days p.i. with an isolate from the heterologous cluster and were necropsied 51 days p.i. The severity of PCV2-associated lesions was reduced in pigs with prior exposure to an isolate from the heterologous cluster in comparison with singly inoculated pigs. Results indicate that the virulence of PCV2a and PCV2b isolates is not different in the conventional SPF pig model; however, the virulence of isolates within the same cluster differs. Increased virulence as reported to be associated with PCV2b isolates in the field was not observed under the conditions of this study. Moreover, cross-protection between PCV2a and PCV2b exists. INTRODUCTIONPorcine circovirus (PCV) is a small, circular, nonenveloped, single-stranded DNA virus (Tischer et al., 1982) that belongs to the genus Circovirus of the family Circoviridae (Todd et al., 2005). To date, two types of PCV have been recognized (Allan et al., 1998;Hamel et al., 1998;Morozov et al., 1998) in pigs: the non-pathogenic PCV type 1 (PCV1) and the pathogenic PCV type 2 (PCV2), which is the aetiological agent of porcine circovirusassociated disease (PCVAD). Previously, phylogenetic analyses have shown that PCV2 isolates can be further divided into two main clusters (Larochelle et al., 2002;Mankertz et al., 2000;Olvera et al., 2007) now commonly referred to as PCV2a and PCV2b (Gagnon et al., 2007).Systemic PCV2 infection, which is also known as postweaning multisystemic wasting syndrome (PMWS), is characterized clinically by wasting or decreased weight gain, enlarged lymph nodes and dyspnoea (Harding & Clark, 1997;Opriessnig et al., 2007). The hallmark microscopic lesions of systemic PCV2 infection are lymphoid depletion and granulomatous lymphadenitis associated with the presence of PCV2 antigen or nucleic acids (Sorden, 2000). Systemic PCV2 infection or PMWS was initially observed in a Canadian high-health-statusThe GenBank/EMBL/DDBJ accession numbers for the complete genomic sequ...

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“…Methods and models for this analysis are described by Detilleux (2011). Studies by Doeschl-Wilson et al (2009), Ait-Ali et al (2007, Vincent et al (2006), Opriessnig et al (2006) and Halbur et al (1998) suggest differences in host genetic response with respect to porcine reproductive and respiratory syndrome and postweaning multisystemic wasting syndrome in view of breeding for improved resistance.…”

Section: New Phenotypesmentioning

confidence: 99%

New phenotypes for new breeding goals in pigs

Merks¹,

Mathur²,

Knol³

2012

Animal

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Pig breeders in the past have adopted their breeding goals according to the needs of the producers, processors and consumers and have made remarkable genetic improvements in the traits of interest. However, it is becoming more and more challenging to meet the market needs and expectations of consumers and in general of the citizens. In view of the current and future trends, the breeding goals have to include several additional traits and new phenotypes. These phenotypes include (a) vitality from birth to slaughter, (b) uniformity at different levels of production, (c) robustness, (d) welfare and health and (e) phenotypes to reduce carbon footprint. Advancements in management, genomics, statistical models and other technologies provide opportunities for recording these phenotypes. These new developments also provide opportunities for making effective use of the new phenotypes for faster genetic improvement to meet the newly adapted breeding goals.

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Genetic and experimental comparison of porcine circovirus type 2 (PCV2) isolates from cases with and without PCV2-associated lesions provides evidence for differences in virulence

Cited by 86 publications

References 46 publications

Singular PCV2a or PCV2b infection results in apoptosis of hepatocytes in clinically affected gnotobiotic pigs

Singular PCV2a or PCV2b infection results in apoptosis of hepatocytes in clinically affected gnotobiotic pigs

Differences in virulence among porcine circovirus type 2 isolates are unrelated to cluster type 2a or 2b and prior infection provides heterologous protection

New phenotypes for new breeding goals in pigs

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