1887

Abstract

Recently, a novel PCV species (PCV3) has been detected in cases associated with sow mortality, lesions consistent with porcine dermatitis and nephropathy syndrome, reproductive failure and multisystemic inflammation. The pathogenesis and clinical significance of PCV3 is still unclear. In this study, we investigated the immunopathogenesis of PCV3 in CD/CD pigs. Four treatment groups, PCV3 (=6), PCV3-KLH (=6), control (=3) and control-KLH (=3), were included with PCV3-positive tissue homogenate (gc=3.38×10 ml and gc=1.04×10 ml), confirmed by quantitative PCR (qPCR) and next-generation sequencing. Clinical signs, viremia, viral shedding, systemic cytokines, humoral (IgG) and T-cellular response were evaluated for 42 days. At necropsy, tissues were collected for histological evaluation and PCV3 detection by qPCR and hybridization. No significant clinical signs were observed through the study. Viremia was detected in both PCV3-inoculated groups from 3 days post-inoculation (p.i.) until the end of the study. Nasal shedding was detected from 3 to 28 days p.i. and faecal shedding was transient. PCV3 induced an early (7 days p.i.) and sustained (42 days p.i.) IgG response. No significant T-cell response was observed. Histological evaluation demonstrated lesions consistent with multisystemic inflammation and perivasculitis. All tissues evaluated were positive by qPCR and virus replication was confirmed by positive hybridization. This study demonstrated the potential role of PCV3 in subclinical infection, producing a mild, multisystemic inflammatory response, prolonged viremia detectable for 42 days p.i., presence of IgG humoral response and viral shedding in nasal secretions. More research is required to understand and elucidate potential co-factors necessary in the manifestation and severity of clinical disease.

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/content/journal/jgv/10.1099/jgv.0.001502
2020-11-18
2020-12-04
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References

  1. Allan G, Krakowka S, Ellis J, Charreyre C. Discovery and evolving history of two genetically related but phenotypically different viruses, porcine circoviruses 1 and 2. Virus Res 2012; 164:4–9 [CrossRef][PubMed]
    [Google Scholar]
  2. Allan GM, Kennedy S, McNeilly F, Foster JC, Ellis JA et al. Experimental reproduction of severe wasting disease by co-infection of pigs with porcine circovirus and porcine parvovirus. J Comp Pathol 1999; 121:1–11 [CrossRef][PubMed]
    [Google Scholar]
  3. Palinski R, Piñeyro P, Shang P, Yuan F, Guo R et al. A novel porcine circovirus distantly related to known circoviruses is associated with porcine dermatitis and nephropathy syndrome and reproductive failure. J Virol 2017; 91: [CrossRef][PubMed]
    [Google Scholar]
  4. Phan TG, Giannitti F, Rossow S, Marthaler D, Knutson TP et al. Detection of a novel circovirus PCV3 in pigs with cardiac and multi-systemic inflammation. Virol J 2016; 13:184 [CrossRef][PubMed]
    [Google Scholar]
  5. Chen GH, Mai KJ, Zhou L, Wu RT, Tang XY et al. Detection and genome sequencing of porcine circovirus 3 in neonatal pigs with congenital tremors in South China. Transbound Emerg Dis 2017; 64:1650–1654 [CrossRef][PubMed]
    [Google Scholar]
  6. Kwon T, Yoo SJ, Park CK, Lyoo YS. Prevalence of novel porcine circovirus 3 in Korean pig populations. Vet Microbiol 2017; 207:178–180 [CrossRef][PubMed]
    [Google Scholar]
  7. Franzo G, Legnardi M, Hjulsager CK, Klaumann F, Larsen LE et al. Full-genome sequencing of porcine circovirus 3 field strains from Denmark, Italy and Spain demonstrates a high within-Europe genetic heterogeneity. Transbound Emerg Dis 2018; 65:602–606 [CrossRef][PubMed]
    [Google Scholar]
  8. Kedkovid R, Woonwong Y, Arunorat J, Sirisereewan C, Sangpratum N et al. Porcine circovirus type 3 (PCV3) infection in grower pigs from a Thai farm suffering from porcine respiratory disease complex (PRDC). Vet Microbiol 2018; 215:71–76 [CrossRef][PubMed]
    [Google Scholar]
  9. Tochetto C, Lima DA, Varela APM, Loiko MR, Paim WP et al. Full-Genome sequence of porcine circovirus type 3 recovered from serum of sows with stillbirths in Brazil. Transbound Emerg Dis 2018; 65:5–9 [CrossRef][PubMed]
    [Google Scholar]
  10. Vargas-Bermudez DS, Campos FS, Bonil L, Mogollon D, Jaime J. First detection of porcine circovirus type 3 in Colombia and the complete genome sequence demonstrates the circulation of PCV3a1 and PCV3a2. Vet Med Sci 2019; 5:182–188 [CrossRef][PubMed]
    [Google Scholar]
  11. Arruda B, Piñeyro P, Derscheid R, Hause B, Byers E et al. PCV3-associated disease in the United States swine herd. Emerg Microbes Infect 2019; 8:684–698 [CrossRef][PubMed]
    [Google Scholar]
  12. Zheng S, Shi J, Wu X, Peng Z, Xin C et al. Presence of torque teno Sus virus 1 and 2 in porcine circovirus 3-positive pigs. Transbound Emerg Dis 2018; 65:327–330 [CrossRef][PubMed]
    [Google Scholar]
  13. Zhai SL, Zhou X, Zhang H, Hause BM, Lin T et al. Comparative epidemiology of porcine circovirus type 3 in pigs with different clinical presentations. Virol J 2017; 14:222 [CrossRef][PubMed]
    [Google Scholar]
  14. Kedkovid R, Woonwong Y, Arunorat J, Sirisereewan C, Sangpratum N et al. Porcine circovirus type 3 (PCV3) shedding in sow colostrum. Vet Microbiol 2018; 220:12–17 [CrossRef][PubMed]
    [Google Scholar]
  15. Zou Y, Zhang N, Zhang J, Zhang S, Jiang Y et al. Molecular detection and sequence analysis of porcine circovirus type 3 in sow sera from farms with prolonged histories of reproductive problems in Hunan, China. Arch Virol 2018; 163:2841–2847 [CrossRef][PubMed]
    [Google Scholar]
  16. Klaumann F, Correa-Fiz F, Sibila M, Núñez JI, Segalés J. Infection dynamics of porcine circovirus type 3 in longitudinally sampled pigs from four Spanish farms. Vet Rec 2019; 184:619 [CrossRef][PubMed]
    [Google Scholar]
  17. Fu X, Fang B, Ma J, Liu Y, Bu D et al. Insights into the epidemic characteristics and evolutionary history of the novel porcine circovirus type 3 in southern China. Transbound Emerg Dis 2018; 65:e296–e303 [CrossRef][PubMed]
    [Google Scholar]
  18. Woźniak A, Miłek D, Bąska P, Stadejek T. Does porcine circovirus type 3 (PCV3) interfere with porcine circovirus type 2 (PCV2) vaccine efficacy?. Transbound Emerg Dis 2019; 66:1454–1461 [CrossRef][PubMed]
    [Google Scholar]
  19. Zhang S, Wang D, Jiang Y, Li Z, Zou Y et al. Development and application of a baculovirus-expressed capsid protein-based indirect ELISA for detection of porcine circovirus 3 IgG antibodies. BMC Vet Res 2019; 15:79 [CrossRef][PubMed]
    [Google Scholar]
  20. Deng J, Li X, Zheng D, Wang Y, Chen L et al. Establishment and application of an indirect ELISA for porcine circovirus 3. Arch Virol 2018; 163:479–482 [CrossRef][PubMed]
    [Google Scholar]
  21. Mora-Díaz J, Piñeyro P, Shen H, Schwartz K, Vannucci F et al. Isolation of PCV3 from perinatal and reproductive cases of PCV3-Associated disease and in vivo characterization of PCV3 replication in CD/CD growing pigs. Viruses 2020; 12:219 [CrossRef][PubMed]
    [Google Scholar]
  22. Classen DC, Morningstar JM, Shanley JD. Detection of antibody to murine cytomegalovirus by enzyme-linked immunosorbent and indirect immunofluorescence assays. J Clin Microbiol 1987; 25:600–604 [CrossRef][PubMed]
    [Google Scholar]
  23. Klaumann F, Franzo G, Sohrmann M, Correa-Fiz F, Drigo M et al. Retrospective detection of porcine circovirus 3 (PCV-3) in pig serum samples from Spain. Transbound Emerg Dis 2018; 65:1290–1296 [CrossRef][PubMed]
    [Google Scholar]
  24. Sun J, Wei L, Lu Z, Mi S, Bao F et al. Retrospective study of porcine circovirus 3 infection in China. Transbound Emerg Dis 2018; 65:607–613 [CrossRef][PubMed]
    [Google Scholar]
  25. Fux R, Söckler C, Link EK, Renken C, Krejci R et al. Full genome characterization of porcine circovirus type 3 isolates reveals the existence of two distinct groups of virus strains. Virol J 2018; 15:25 [CrossRef][PubMed]
    [Google Scholar]
  26. Krakowka S, Ellis JA, McNeilly F, Ringler S, Rings DM et al. Activation of the immune system is the pivotal event in the production of wasting disease in pigs infected with porcine circovirus-2 (PCV-2). Vet Pathol 2001; 38:31–42 [CrossRef][PubMed]
    [Google Scholar]
  27. Opriessnig T, Halbur PG. Concurrent infections are important for expression of porcine circovirus associated disease. Virus Res 2012; 164:20–32 [CrossRef][PubMed]
    [Google Scholar]
  28. Allen AR, McHale J, Smith J, Cook HT, Karkar A et al. Endothelial expression of VCAM-1 in experimental crescentic nephritis and effect of antibodies to very late antigen-4 or VCAM-1 on glomerular injury. J Immunol 1999; 162:5519–5527[PubMed]
    [Google Scholar]
  29. Harms PA, Sorden SD, Halbur PG, Bolin SR, Lager KM et al. Experimental reproduction of severe disease in CD/CD pigs concurrently infected with type 2 porcine circovirus and porcine reproductive and respiratory syndrome virus. Vet Pathol 2001; 38:528–539 [CrossRef][PubMed]
    [Google Scholar]
  30. Drolet R, Larochelle R, Morin M, Delisle B, Magar R. Detection rates of porcine reproductive and respiratory syndrome virus, porcine circovirus type 2, and swine influenza virus in porcine proliferative and necrotizing pneumonia. Vet Pathol 2003; 40:143–148 [CrossRef][PubMed]
    [Google Scholar]
  31. Nieto D, Kekarainen T, Aramouni M, Segales J. Torque teno Sus virus 1 and 2 distribution in tissues of porcine circovirus type 2-systemic disease affected and age-matched healthy pigs. Vet Microbiol 2013; 163:364–367 [CrossRef][PubMed]
    [Google Scholar]
  32. Niederwerder MC, Jaing CJ, Thissen JB, Cino-Ozuna AG, McLoughlin KS et al. Microbiome associations in pigs with the best and worst clinical outcomes following co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2). Vet Microbiol 2016; 188:1–11 [CrossRef][PubMed]
    [Google Scholar]
  33. Franzo G, Kekarainen T, Llorens A, Correa-Fiz F, Segales J. Exploratory metagenomic analyses of periweaning failure-to-thrive syndrome-affected pigs. Vet Rec 2019; 184:25 [CrossRef][PubMed]
    [Google Scholar]
  34. Segales J. Porcine circovirus type 2 (PCV2) infections: clinical signs, pathology and laboratory diagnosis. Virus Res 2012; 164:10–19 [CrossRef][PubMed]
    [Google Scholar]
  35. Harding JCS, Baker CD, Tumber A, McIntosh KA, Parker SE et al. Porcine circovirus-2 DNA concentration distinguishes wasting from nonwasting pigs and is correlated with lesion distribution, severity, and nucleocapsid staining intensity. J Vet Diagn Invest 2008; 20:274–282 [CrossRef][PubMed]
    [Google Scholar]
  36. Grau-Roma L, Hjulsager CK, Sibila M, Kristensen CS, López-Soria S et al. Infection, excretion and seroconversion dynamics of porcine circovirus type 2 (PCV2) in pigs from post-weaning multisystemic wasting syndrome (PMWS) affected farms in Spain and Denmark. Vet Microbiol 2009; 135:272–282 [CrossRef][PubMed]
    [Google Scholar]
  37. Opriessnig T, Prickett JR, Madson DM, Shen H-G, Juhan NM et al. Porcine circovirus type 2 (PCV2)-infection and re-inoculation with homologous or heterologous strains: virological, serological, pathological and clinical effects in growing pigs. Vet Res 2010; 41:31 [CrossRef][PubMed]
    [Google Scholar]
  38. Meerts P, Misinzo G, Lefebvre D, Nielsen J, Bøtner A et al. Correlation between the presence of neutralizing antibodies against porcine circovirus 2 (PCV2) and protection against replication of the virus and development of PCV2-associated disease. BMC Vet Res 2006; 2:6 [CrossRef][PubMed]
    [Google Scholar]
  39. Tischer I, Bode L, Peters D, Pociuli S, Germann B. Distribution of antibodies to porcine circovirus in swine populations of different breeding farms. Arch Virol 1995; 140:737–743 [CrossRef][PubMed]
    [Google Scholar]
  40. Piñeyro PE, Kenney SP, Gimenez-Lirola LG, Heffron CL, Matzinger SR et al. Expression of antigenic epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) in a modified live-attenuated porcine circovirus type 2 (PCV2) vaccine virus (PCV1-2a) as a potential bivalent vaccine against both PCV2 and PRRSV. Virus Res 2015; 210:154–164 [CrossRef][PubMed]
    [Google Scholar]
  41. Cleveland SM, Buratti E, Jones TD, North P, Baralle F et al. Immunogenic and antigenic dominance of a nonneutralizing epitope over a highly conserved neutralizing epitope in the gp41 envelope glycoprotein of human immunodeficiency virus type 1: its deletion leads to a strong neutralizing response. Virology 2000; 266:66–78 [CrossRef][PubMed]
    [Google Scholar]
  42. Ostrowski M, Galeota JA, Jar AM, Platt KB, Osorio FA et al. Identification of neutralizing and nonneutralizing epitopes in the porcine reproductive and respiratory syndrome virus GP5 ectodomain. J Virol 2002; 76:4241–4250 [CrossRef][PubMed]
    [Google Scholar]
  43. Jin J, Park C, Cho S-H, Chung J. The level of decoy epitope in PCV2 vaccine affects the neutralizing activity of sera in the immunized animals. Biochem Biophys Res Commun 2018; 496:846–851 [CrossRef][PubMed]
    [Google Scholar]
  44. Darwich L, Segales J, Domingo M, Mateu E. Changes in CD4(+), CD8(+), CD4(+) CD8(+), and immunoglobulin M-positive peripheral blood mononuclear cells of postweaning multisystemic wasting syndrome-affected pigs and age-matched uninfected wasted and healthy pigs correlate with lesions and porcine circovirus type 2 load in lymphoid tissues. Clin Diagn Lab Immunol 2002; 9:236–242 [CrossRef][PubMed]
    [Google Scholar]
  45. Steiner E, Balmelli C, Gerber H, Summerfield A, McCullough K. Cellular adaptive immune response against porcine circovirus type 2 in subclinically infected pigs. BMC Vet Res 2009; 5:45 [CrossRef][PubMed]
    [Google Scholar]
  46. Liu J, Chen I, Du Q, Chua H, Kwang J. The ORF3 protein of porcine circovirus type 2 is involved in viral pathogenesis in vivo. J Virol 2006; 80:5065–5073 [CrossRef][PubMed]
    [Google Scholar]
  47. Liu J, Chen I, Kwang J. Characterization of a previously unidentified viral protein in porcine circovirus type 2-infected cells and its role in virus-induced apoptosis. J Virol 2005; 79:8262–8274 [CrossRef][PubMed]
    [Google Scholar]
  48. Karuppannan AK, Kwang J. ORF3 of porcine circovirus 2 enhances the in vitro and in vivo spread of the of the virus. Virology 2011; 410:248–256 [CrossRef][PubMed]
    [Google Scholar]
  49. Yang JS, Song DS, Kim SY, Lyoo KS, Park BK. Detection of porcine circovirus type 2 in feces of pigs with or without enteric disease by polymerase chain reaction. J Vet Diagn Invest 2003; 15:369–373 [CrossRef][PubMed]
    [Google Scholar]
  50. Tico G, Segales J, Martinez J. The blurred border between porcine circovirus type 2-systemic disease and porcine respiratory disease complex. Vet Microbiol 2013; 163:242–247 [CrossRef][PubMed]
    [Google Scholar]
  51. Baro J, Segales J, Martinez J. Porcine circovirus type 2 (PCV2) enteric disease: an independent condition or part of the systemic disease?. Vet Microbiol 2015; 176:83–87 [CrossRef][PubMed]
    [Google Scholar]
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