Coinfection in Porcine Circovirus Type 2

The pathogenesis of porcine circovirus type 2 (PCV2) infections in pigs is still not completely understood. PCV2 has a tropism for lymphoid tissues where it is associated with depletion of follicles and histiocytic infiltration thereby accumulating in large numbers mainly in the cytoplasm of macrophages (1).PCV2 belongs to the Circoviridae family and is one of the smallest known single-stranded DNA viruses (2). Since the virus lacks its own enzymes, viral DNA intermediates are generated in host cell nuclei and depend on host cell enzymes present in the synthesis (S) phase of the cell cycle for completion of the replication cycle in vitro(3). Virions are assembled in both nuclei and cytoplasm and released from infected cells in the absence of viral cytopathic effects. Little is known about the requirements for the growth of PCV2 in vivo.

It has been reported that new cellular DNA synthesis is the only in vivo prerequisite for PCV2 replication (4).It has been demonstrated that treatment of porcine kidney-15 cell cultures with IFN-γ causes a 20 times higher production of PCV2 progeny (5). There is field evidence and experimental proof that coinfecting pathogens trigger PCV2-infection to progress to full blown clinical disease. Coinfecting pathogens may increase PCV2 in two ways: by inducing release of host IFN-γ in response to the co-infecting pathogen and by (2) initiating host cell replication especially of cells of the immune system thereby enhancing PCV2 replication.

A retrospective analysis of 484 PMWS cases in the Midwest United States revealed that PCV2 alone was found in only 9 of 484 (1.9%) cases investigated (6). Porcine reproductive and respiratory syndrome virus (PRRSV) was detected in 251 of 484 (51.9%) cases, M. hyopneumoniae was found in combination with PCV2 in 172 of 484 (35.5%) cases, and Swine influenza virus (SIV) was detected in 26 of 484 (5.4%) cases  (6). A case control study done on pigs with a clinical history of wasting and microscopic lesions characteristic of PCVAD (n = 31) and on control pigs without clinical signs or microscopic lesions typical of PCVAD (n = 56) revealed that among all viruses tested [PCV2, PRRSV, porcine parvovirus (PPV), porcine enterovirus types 1-3, SIV, porcine respiratory coronavirus (PRCV), transmissible gastroenteritis virus (TGEV), porcine endogenous retrovirus, porcine lymphotropic herpesvirus type 1, and bovine virus diarrhea virus] PCV2 had the strongest association with PCVAD; however, the risk for clinical PCVAD was much higher if the pig was PCV2/PRRSV coinfected (7). A case-control study to investigate the presence of coinfections in the Netherlands had similar results: 60 clinically affected pigs from 20 different farms and 180 pigs without clinical signs were compared. Concurrent PRRSV infection was found in 83% of the PMWS-affected pigs and in 35% of the pigs from PMWS-free herds (8). In 2007 a study investigating PCV2 and coinfection status of 3-, 9-, 16-, and 24-week-old pigs from 41 different 1-, 2-, and 3-site production systems was published (9). It was found that compared with PCV2-negative pigs, PCV2-positive pigs were more likely to have SIV type A and M. hyopneumoniae infections and sample-to-positive ratios for SIV H1N1 from 0.50 to 0.99; also, PCV2-positive pigs had higher serum anti-PRRSV antibody titers and more severe lung tissue damage. Infection with SIV was more likely in 3-week-old PCV2-positive pigs and evidence of systemic disease was greater in 16-week-old PCV2-positive pigs than in their PCV2-negative counterparts. The overall conclusion of this study was that in PCV2-positive pigs, coinfections with SIV, M. hyopneumoniae, and PRRSV are important, having the greatest effect in the early to late nursery phase and in 3-site production systems.(9)

Based on field and experimental evidence it seems clear that PCV2 infection can be upregulated by concurrent infections. However, the exact mechanism of this is not well understood and more research is clearly needed. Comparison between experiments is difficult as most experiments have been conducted by different research groups, using different PCV2 isolates at different titers, and using different pig types (CD, CD/CD, gnotobiotic, SPF, conventional) with different ages at infection (range from 1 to 56 days). In most controlled experiments, concurrent infection increased levels of PCV2 while the concurrent pathogen appeared not to be upregulated. The majority of the studies were conducted by coinfecting the pigs at the same time. It is of interest, that in one study where PCV2 was given first (subclinical PCV2 infection in sows and their piglets) the coinfecting pathogen (PEDV) and not PCV2 was up-regulated. Timing of coinfections may be an important factor and probably needs to be further investigated in order to gain more insights into the pathogenicity of PCV2 infection. Based on the current knowledge, it appears important that practitioners do a thorough diagnostic investigation on herds where PCVAD is a recurrent problem.

References

1. Sorden SD. Update on porcine circovirus and postweaning multisystemic wasting syndrome (PMWS). Swine Hlth Prod. 2000;8:133-136.

2. Todd D, Bendinelli M, Biagini P, Hino S, Mankertz A, Mishiro S, Niel C, Okamoto H, Raidal S, Ritchie BW, Teo G. Circoviridae. 2005;Eighth report of the international committee on taxonomy of viruses:327-334.

3. Tischer I, Peters D, Rasch R, Pociuli S. Replication of porcine circovirus: induction by glucosamine and cell cycle dependence. Arch Virol. 1987;96:39-57.

4. Kennedy S, Moffett D, McNeilly F, Meehan B, Ellis J, Krakowka S, Allan GM. Reproduction of lesions of postweaning multisystemic wasting syndrome by infection of conventional pigs with porcine circovirus type 2 alone or in combination with porcine parvovirus. J Comp Pathol. 2000;122:9-24.

5. Meerts P, Misinzo G, Nauwynck HJ. Enhancement of porcine circovirus 2 replication in porcine cell lines by IFN-gamma before and after treatment and by IFN-alpha after treatment. J Interferon Cytokine Res. 2005;25:684-693.

6. Pallarés FJ, Halbur PG, Opriessnig T, Sorden SD, Villar D, Janke BH, Yaeger MJ, Larson DJ, Schwartz KJ, Yoon KJ, Hoffman LJ. Porcine circovirus type 2 (PCV-2) coinfections in US field cases of postweaning multisystemic wasting syndrome (PMWS). J Vet Diagn Invest. 2002;14:515-519.

7. Pogranichniy RM, Yoon KJ, Harms PA, Sorden SD, Daniels M. Case-control study on the association of porcine circovirus type 2 and other swine viral pathogens with postweaning multisystemic wasting syndrome. J Vet Diagn Invest. 2002;14:449-456.

8. Wellenberg GJ, Stockhofe-Zurwieden N, Boersma WJ, De Jong MF, Elbers AR. The presence of co-infections in pigs with clinical signs of PMWS in The Netherlands: a case-control study. Res Vet Sci. 2004;77:177-184.

9. Dorr PM, Baker RB, Almond GW, Wayne SR, Gebreyes WA. Epidemiologic assessment of porcine circovirus type 2 coinfection with other pathogens in swine. J Am Vet Med Assoc. 2007;230:244-250.


This presentation was given at the Pork Expo 2010 e V Fórum Internacional de Suinocultura, Curitiba, Brazil and was provided to Engormix.com courtesy of the organizing committee.