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Virologica Sinica logoLink to Virologica Sinica
. 2014 Jun 17;29(3):176–182. doi: 10.1007/s12250-014-3431-0

Unusual outcome of in utero infection and subsequent postnatal super-infection with different PCV2b strains

Dipongkor Saha 1,6, Uladzimir U Karniychuk 1,8, Liping Huang 1,7, Marc Geldhof 1, Merijn Vanhee 1,3, David J Lefebvre 1,4, Peter Meerts 1,5, Richard Ducatelle 2, Jan V Doorsselaere 3, Hans J Nauwynck 1,
PMCID: PMC8206427  PMID: 24950783

Abstract

VC2002, isolated from postweaning multisystemic wasting syndrome (PMWS)-affected pig, is a mixture of two porcine circovirus genotype 2b (PCV2b) viruses, K2 and K39. Preliminary experiments disclosed short-term adverse effects of K39, but not K2, on porcine foetuses. These findings led to the hypothesis that infection of immuno-incompetent foetuses with K2 confers a status of immunotolerance, and postnatal super-infection with K39 triggers PMWS. To explore this hypothesis, nine 55-day-old foetuses were inoculated in utero (three with K2-104.3TCID50, three with K39-104.3TCID50 and three with medium), and foeto-pathogenicity examined. At 21 days post-inoculation (dpi), K2 did not induce pathology, whereas pathological effects of K39 were evident. Twenty-four 45-day-old foetuses were subsequently inoculated to examine the long-term effect of K2, including six with K2-high dose-104.3TCID50, six with K2-low dose-102.3TCID50 and 12 mock-inoculated controls. Both doses resulted in five mummified foetuses and one live-born piglet each (69dpi). K2 was recovered from all mummies. K2 and K2-specific antibodies were not detected in serum of the two live-born piglets at birth, indicating full control of K2 infection. The K2-low dose-infected piglet was immunostimulated at day 2, but not the K2-high dose-infected piglet. Both non-stimulated and stimulated K2-infected piglets were super-inoculated with K39 at day 6 or 8 (taken as 0 days post super-inoculation). Low viral replication was observed in the non-stimulated K2-K39 piglet (up to 103.3TCID50/g; identified as K39). In contrast, viral replication was extremely high in the stimulated K2-K39 piglet (up to 105.6TCID50/g) and identified as K2, indicating that K2 infection is controlled during foetal life, but emerges after birth upon immunostimulation. However, none of the piglets showed any signs of PMWS.

Keywords: PCV2, immunotolerance, PMWS, porcine foetuses

References

  1. Brunborg I M, Jonassen C M, Moldal T, Bratberg B, Lium B, Koenen F, Schönheit J. Association of myocarditis with high viral load of porcine circovirus type 2 in several tissues in cases of fetal death and high mortality in piglets. A case study. J Vet Diagn Invest. 2007;19:368–375. doi: 10.1177/104063870701900405. [DOI] [PubMed] [Google Scholar]
  2. Gerber P F, Johnson J, Shen H, Striegel D, Xiao C T, Halbur P G, Opriessnig T. Association of concurrent porcine circovirus (PCV) 2a and 2b infection with PCV associated disease in vaccinated pigs. Res Vet Sci. 2013;95:775–781. doi: 10.1016/j.rvsc.2013.06.004. [DOI] [PubMed] [Google Scholar]
  3. Ha Y, Lee Y H, Ahn K K, Kim B, Chae C. Reproduction of postweaning multisystemic wasting syndrome in pigs by prenatal porcine circovirus 2 infection and postnatal porcine parvovirus infection or immunostimulation. Vet Pathol. 2008;45:842–848. doi: 10.1354/vp.45-6-842. [DOI] [PubMed] [Google Scholar]
  4. Lefebvre D J, Costers S, Van Doorsselaere J, Misinzo G, Delputte P L, Nauwynck H J. Antigenic differences among porcine circovirus type 2 strains, as demonstrated by the use of monoclonal antibodies. J Gen Virol. 2008;89:177–187. doi: 10.1099/vir.0.83280-0. [DOI] [PubMed] [Google Scholar]
  5. McNeilly F, McNair I, Mackie D P, Meehan B M, Kennedy S, Moffett D, Ellis J, Krakowka S, Allan G M. Production, characterization and applications of monoclonal antibodies to porcine circovirus 2. Arch Virol. 2001;146:909–922. doi: 10.1007/s007050170124. [DOI] [PubMed] [Google Scholar]
  6. Meehan B M, McNeilly F, McNair I, Walker I, Ellis J A, Krakowka S, Allan G M. Isolation and characterization of porcine circovirus 2 from cases of sow abortion and porcine dermatitis and nephropathy syndrome. Arch Virol. 2001;146:835–842. doi: 10.1007/s007050170152. [DOI] [PubMed] [Google Scholar]
  7. Meerts P, Nauwynck H, Sanchez R, Mateusen B, Pensaert M. Prevalence of porcine circovirus 2 (PCV2)-related wasting on Belgian farms with or without a history of postweaning multisystemic wasting syndrome. Vlaams Diergen Tijds. 2004;73:31–38. [Google Scholar]
  8. Meerts P, Van Gucht S, Cox E, Vandebosch A, Nauwynck H J. Correlation between type of adaptive immune response against porcine circovirus type 2 and level of virus replication. Viral Immunol. 2005;18:333–341. doi: 10.1089/vim.2005.18.333. [DOI] [PubMed] [Google Scholar]
  9. Meerts P, Misinzo G, Lefebvre D, Nielsen J, Bøtner A, Kristensen C S, Nauwynck H J. 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. doi: 10.1186/1746-6148-2-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Saha D, Lefebvre D J, Van Doorsselaere J, Atanasova K, Barbé F, Geldhof M, Karniychuk U U, Nauwynck H J. Pathologic and virologic findings in mid-gestational porcine foetuses after experimental inoculation with PCV2a or PCV2b. Vet Microbiol. 2010;145:62–68. doi: 10.1016/j.vetmic.2010.03.017. [DOI] [PubMed] [Google Scholar]
  11. Saha D, Lefebvre D J, Ducatelle R, Doorsselaere J V, Nauwynck H J. Outcome of experimental porcine circovirus type 1 infections in mid-gestational porcine foetuses. BMC Vet Res. 2011;7:64. doi: 10.1186/1746-6148-7-64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Saha D, Huang L, Bussalleu E, Lefebvre D J, Fort M, Doorsselaere J V, Nauwynck H J. Antigenic subtyping and epitopes’ competition analysis of porcine circovirus type 2 using monoclonal antibodies. Vet Microbiol. 2012;157:13–22. doi: 10.1016/j.vetmic.2011.11.030. [DOI] [PubMed] [Google Scholar]
  13. Saha D, Doorsselaere J V, Nauwynck H J. Instability in vitro of a PCV2 infectious clone containing an insertion between ORF1 and ORF2. Virus Genes. 2012;44:258–261. doi: 10.1007/s11262-011-0693-6. [DOI] [PubMed] [Google Scholar]
  14. Saha D, Lefebvre D J, Ooms K, Huang L, Delputte P L, Van Doorsselaere J, Nauwynck H J. Single amino acid mutations in the capsid switch the neutralization phenotype of porcine circovirus 2. J Gen Virol. 2012;93:1548–1555. doi: 10.1099/vir.0.042085-0. [DOI] [PubMed] [Google Scholar]
  15. Saha D, Del Pozo Sacristán R, Van Renne N, Huang L, Decaluwe R, Michiels A, Rodriguez A L, Rodríguez M J, Durán M G, Declerk I, Maes D, Nauwynck H J. Anti-porcine circovirus type 2 (PCV2) antibody placental barrier leakage from sow to fetus: impact on the diagnosis of intra-uterine PCV2 infection. Virol Sin. 2014;29:136–138. doi: 10.1007/s12250-014-3432-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sanchez R E, Meerts P, Nauwynck H J, Pensaert M B. Change of porcine circovirus 2 target cells in pigs during development from foetal to early postnatal life. Vet Microbiol. 2003;95:15–25. doi: 10.1016/S0378-1135(03)00120-2. [DOI] [PubMed] [Google Scholar]
  17. Sarli G, Morandi F, Panarese S, Bacci B, Ferrara D, Bianco C, Fusaro L, Bacci M L, Galeati G, Dottori M, Bonilauri P, Lelli D, Leotti G, Vila T, Joisel F, Allan G, Benazzi C, Ostanello F. Reproduction in porcine circovirus type 2 (PCV2) seropositive gilts inseminated with PCV2b spiked semen. Acta Vet Scand. 2012;54:51. doi: 10.1186/1751-0147-54-51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Segalés J. Porcine circovirus type 2 (PCV2 infections: clinical signs, pathology and laboratory diagnosis. Virus Res. 2012;164:10–19. doi: 10.1016/j.virusres.2011.10.007. [DOI] [PubMed] [Google Scholar]
  19. Sinkora M, Sun J, Sinkorova J, Christenson R K, Ford S P, Butler J E. Antibody repertoire development in fetal and neonatal piglets. VI. B-cell lymphogenesis occurs at multiple sites with differences in the frequency of in-frame rearrangements. J Immunol. 2003;170:1781–1788. doi: 10.4049/jimmunol.170.4.1781. [DOI] [PubMed] [Google Scholar]
  20. Sinkora M, Butler J E. The ontogeny of the porcine immune system. Dev Comp Immunol. 2009;33:273–283. doi: 10.1016/j.dci.2008.07.011. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Virologica Sinica are provided here courtesy of Wuhan Institute of Virology, Chinese Academy of Sciences

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