The members of this consortium have had an active research programme on PCVDs for the last 7 years and their collective research findings and publications in peer reviewed journals (> 100) represent the major advances in PCVD research and the state of the art.

Porcine circovirus:

Porcine circovirus (PCV) was first identified in 1974 as a contaminant of the continuous pig kidney cell line PK/15 [63]. This virus was later shown to contain a single-stranded, circular DNA genome. A "novel" PCV-like virus was first isolated from pigs with a wasting disease in western Canada in 1998 [17]. Shortly thereafter, similar viruses were isolated from diseased pigs in N America and Europe [1, 2, 57]. These isolates were shown to be antigenically and genomically distinct from PCV isolates and were designated PCV2 viruses, to discern from the previous virus, which was named PCV1 [8]. PCV1 and PCV2 are small (17nm) icosahedral, non-enveloped viruses containing a single-stranded, circular DNA genome and are now classified in the circovirus genus of the family Circoviridae [24, 25, 60, 61, 63, 64]. They show an ambisense genome organisation with 2 major open reading frames for replication and packaging of viral DNA [34, 35, 36, 38, 39, 40, 41, 42, 62]. The exact mechanisms of viral replication and interaction with host factors are still not known. Mechanisms of PCV2 replication and the molecular basis of pathogenesis of the virus will be addressed in Work Package 4 of this project.


Field disease:

A wasting syndrome in Canadian and French pigs was first reported in 1996 and named postweaning multisystemic wasting syndrome (PMWS) [13, 33]. PCV nucleic acid and antigen were demonstrated in abundance in the lesions of affected pigs and subsequent isolation and characterisation of a PCV2 virus from diseased pigs was reported [1, 2, 17, 53]. Since these initial reports of PCV2-associated wasting disease in piglets in Canada and France the disease has been reported in almost all pig producing countries around the world [37, 49, 57]. Gross lesions of PCVD/PMWS include generalised lymphadenopathy, hepatitis, nephritis and pneumonia and typical histological lesions include lymphocytic depletion together with histiocytic and multinucleated giant cell infiltration in lymph nodes, degeneration and necrosis of hepatocytes, and multifocal lymphohistiocytic interstitial pneumonia [1, 26, 53]. The criteria used for the diagnosis of PCVD/PMWS include the existence of compatible clinical signs, presence of characteristic microscopic lesions in lymphoid tissues and detection of PCV2 within these lesions [59]. Reagents and SOPs for diagnosis and detection of PCVD/PMWS will be optimised and harmonised in Work Package 1 of this project.

PCV2 is widespread in pigs throughout the world and retrospective analyses of sera from 1969 onwards have shown the presence of antibody to a PCV2 virus in a high percentage of the sera tested [14, 43, 44, 51, 52, 65]. Retrospective analyses of tissue sections from diseased pigs has shown that sporadic cases of classical PCVD/PMWS have occurred as far back as the early 1986 [51, 55]. Evidence is emerging that PCV2 may play a major role in other porcine disease syndromes, including proliferating and necrotising pneumonia [1,48], reproductive disorders in pigs [31, 66] and porcine dermatitis and nephropathy syndrome (PDNS) [1, 20, 59]. PDNS was first described in S America in 1976, but until recently occurred only sporadically in EU member states. However, outbreaks of PDNS over the past 5 years have spiralled to epidemic proportions in EU member states and elsewhere. A recent survey in UK identified 251 cases (9.6 % of larger pig holdings). In many of these incidents, PDNS progressed from a sporadic to an epizootic form, with a case mortality of 25 to 30%. Mortalities can reach 100%, as has been reported for PDNS outbreaks in Spain. The microscopic lesions of PDNS are indicative of an immune complex-mediated disease, typically those of a type III hypersensitivity reaction. Nevertheless, epidemiological evidence suggests that PDNS is an infectious disease. The emergence of epidemic PDNS in recent years parallels the appearance of PCVD/PMWS leading to speculation that this syndrome is also PCV2-related [45]. However, to date, no consistent model of experimental production of PDNS has been developed. This will be addressed in Work Package 5 of this project. PCV2 is not a new virus and PCVD/PMWS is not a new disease. It is not known why sporadic PCVD/PMWS has emerged during the last decade as a global epizootic. Information generated in Work Package 2 of this project will be important in answering this, and other questions related to PCVD/PMWS epizootiology.


Experimental infections:

Clinical disease, and gross and histological lesions consistent with PCVD/PMWS have been reproduced following experimental infection of gnotobiotic, colostrum-deprived (CD) and colostrum-fed (CF) piglets with PCV2 [3, 4, 5, 6, 7, 9, 10, 11, 12, 18, 21, 22, 26, 28, 29, 30, 50, 54]. Consistent reproduction of clinical disease in an experimental model seems to require PCV2 infection plus modulation of the immune system by either co-infection with other viruses (porcine parvovirus (PPV)/porcine reproductive and respiratory disease virus (PRRSV) or the use of non-infectious immune modulators [3, 4, 5, 22, 26, 28, 29, 30, 50]. Recent studies using a gnotobiotic model have shown that inoculation of pigs with PCV2 alone plus a non-specific stimulation of immune system results in clinical PCVD/PMWS in 100% of the inoculates [28]. To date, this remains the only 100% disease model, which uses PCV2 as the only infectious agent. However, reproducible clinical disease can be achieved by the co-inoculation of CD pigs with PCV2 and PPV [3, 7], or cloned PCV2 DNA with PPV [unpublished]. Also experimental in-utero infection of porcine foetuses has resulted in gross and histological lesions in the inoculated foetuses, that vary in severity, dependent on the state of gestation of the foetus when inoculated [56]. Stimulation of the immune system of young pigs in current husbandry practises can be multifactorial and PCVD/PMWS is now considered as a multifactorial syndrome where PCV2 is essentially. Mechanisms of PCV2 pathogenesis will be elucidated in Work Packages 5 and 6 of this project.


Immunology and Immunopathogenesis:

Infected pigs seroconvert to PCV2, however the specific roles of the different immune compartments in protection against disease is unknown [27]. Studies have shown that PCV2 accumulates in macrophages and dendritic cells. This is likely to be a pivotal event in the pathogenesis of the disease. In-vivo studies on tissues from PMWS-affected pigs have shown that macrophages and/or dendritic cells contain large amounts of PCV2 antigen [18, 28, 29, 53]. Recent in-vitro studies have confirmed that PCV2 does not replicate in these cell types [19]. However, importantly, PCV2 infectivity was not reduced following infection of macrophages and in-vitro culture for up to 8 days. In vitro studies have revealed potentially immunoregulatory sequences in the genome of PCV2 that inhibits induction of IFN-alpha production [23].

Field and experimental studies have shown significant changes in the subpopulations of blood peripheral mononuclear cells of diseased pigs. These changes were characterised by lymphopenia, increase of circulating monocytes, reduction of T cells (mainly CD4+ and/or CD8+, as well as double positive cells) and B lymphocytes when compared with clinically healthy, non-PCV2 infected pigs [16, 47, 58]. In addition, more recent work have shown cytokine mRNA alterations in PMWS affected pigs, which were characterized by an over expression of IL-10 mRNA in thymus and IFN-gamma mRNA in tonsils, and by decreases of several cytokines in other lymphoid tissues [15].

All together, these immunopathological findings in PMWS affected pigs suggest an inability to mount an effective immune response. However, it still remains unclear how this virus acts upon the immune system of infected pigs, especially during the early phases of infection. This will be addressed in Work Packages 5 and 6 of this project.


Control of PCVDs:

Currently very little is known about control of PCVDs. Recent field studies have indicated that a "20-point plan" of improved husbandry measures may sometimes, but not always, limit the disease impact in affected herds [32]. Importantly, field observations by veterinarians and producers suggest that susceptibility/resistance to PCVD/PMWS may be influenced by the genetics or breed of the host, specifically in regard to the boar lines used. None of these “observations” have been scientifically evaluated or assessed. This will be addressed in Work Package 3 of this project. In addition, on some farms the use of feed additives and alterations in feeding regimes have had a beneficial effect on PCVD/PMWS. However, on other farms this has had no effect. This will be addressed in Work Package 7 of this project. To date, no commercial vaccines are available for PCVD. Strategies for the control of PCVDs will be developed through the collaborative efforts of all partners and particularly through data obtained from Work Packages 2, 3, 5, 6, 7 and 8. Information generated within all of the above Work Packages will be disseminated through Work Package 9 of the project.


Summary:

Since the initiation of the two research projects on PCVD under Framework 5, a great deal of basic information on the pathogenesis, epidemiology and replication of PCV2 has been generated and a new generation of biological and procedures for the study of this disease have been prepared. This information and these biological and procedures will serve as a sound platform for further research in this proposed project by an enhanced new multidisciplinary consortium. The new consortium combines the existing strengths of the partners from the two previous projects with expertise in epizootiology, nutrition, porcine genetics, bacteriology and information dissemination.


References:

1. Albina E, Truong C, Hutet E, Blanchard P, Cariolet R, L'Hospitalier R, Mahe D, Allee C, Morvan H, Amenna N, Le Dimna M, Madec F and Jestin A. An experimental model for post-weaning multisystemic wasting syndrome (PMWS) in growing piglets. Journal of Comparative Pathology 2001; 125: 292-303.
2. Allan GM, Phenix K, Todd D and McNulty M. Some biological and physico-chemical properties or porcine circovirus. Journal of Veterinary Medicine B 1994; 41: 17-26.
3. Allan GM, McNeilly F, Foster JC, Adair BM. Infection of leucocyte cell cultures derived from different species with pig circovirus. Veterinary Microbiology 1994; 41(3):267-279.
4. Allan GM, Mackie DP, McNair J, Adair BM, McNulty MS. Production, preliminary characterisation and applications of monoclonal antibodies to porcine circovirus. Veterinary Immunology and Immunopathology 1994 Nov; 43(4):357-371.
5. Allan GM, McNeilly F, Cassidy JP, Reilly GA, Adair B, Ellis WA, McNulty MS. Pathogenesis of porcine circovirus; experimental infections of colostrum deprived piglets and examination of pig foetal material. Veterinary Microbiology 1995; 44(1):49-64.
6. Allan GM, McNeilly F, Kennedy S, Daft B, Clarke EG, Ellis JA, Haines DM, Meehan BM, Adair BM. Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe. Journal of Veterinary Diagnostic Investigation 1998; 10(1):3-10.
7. Allan G, Meehan B, Todd D, Kennedy S, McNeilly F, Ellis J, Clark EG, Harding J, Espuna E, Botner A, Charreyre C. Novel porcine circoviruses from pigs with wasting disease syndromes. Veterinary Record 1998; 142(17):467-468.
8. Allan GM, McNeilly F, Meehan BM, Kennedy S, Mackie DP, Ellis JA, Clark EG, Espuña E, Saubi N, Riera P, Botner A and Charreyre CE. Isolation and characterisation of circoviruses from pigs with wasting syndromes in Spain, Denmark and Northern Ireland. Veterinary Microbiology 1999; 66: 115-123.
9. Allan GM, Kennedy S, McNeilly F, Foster JC, Ellis JA, Krakowka SJ, Meehan BM and Adair BM. Experimental reproduction of severe wasting disease by co-infection of pigs with porcine circovirus and porcine parvovirus. Journal of Comparative Pathology 1999; 121: 1-11.
10. Allan GM, McNeilly F, Meehan BM, Ellis JA, Connor TJ, McNair I, Krakowka S, Kennedy S. A sequential study of experimental infection of pigs with porcine circovirus and porcine parvovirus: immunostaining of cryostat sections and virus isolation. Journal of Veterinary Medicine B Infect Dis Vet Public Health 2000; 47(2):81-94.
11. Allan GM, McNeilly F, Kennedy S, Meehan B, Ellis J, Krakowka S. Immunostimulation, PCV-2 and PMWS. Veterinary Record 2000; 147(6):170-171.
12. Allan GM, McNeilly E, Kennedy S, Meehan B, Moffett D, Malone F, Ellis J and Krakowka S. PCV-2-associated PDNS in Northern Ireland in 1990. Porcine dermatitis and nephropathy syndrome. Veterinary Record 2000; 146:711-712.
13. Allan GM, McNeilly F, Ellis J, Krakowka S, Meehan B, McNair I, Walker I, and Kennedy S. Experimental infection of colostrum deprived piglets with porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) potentiates PCV2 replication. Archives of Virology 2000; 145: 2421-2429.
14. Allan GM and Ellis JA. 2000. Porcine circoviruses: a review. Journal of Veterinary Diagnostic Investigation; 12: 3-14.
15. Allan GM, McNeilly F, McNair I, Curran MD, Walker I, Ellis J, Konoby C, Kennedy S, Meehan B. Absence of evidence for porcine circovirus type 2 in cattle and humans, and lack of seroconversion or lesions in experimentally infected sheep. Archives of Virology 2000; 145(4):853-857.
16. Allan GM, McNeilly F, McNair I, O’Connor M, Meehan B, Gilpin D, Ellis J, Townsend H, Lasagna C, Boriosi G and Krakowka S. Neonatal vaccination for Mycoplasma hyopneumoniae and post-weaning multisystemic wasting syndrome: a field trial. Pig Journal 2001; 48: 34-41.
17. Allan GM, McNeilly F, Meehan B, Kennedy S, Johnston D, Ellis J, Krakowka S, Fossum C, Wattrang E and Wallgren P. Reproduction of PMWS with a 1993 Swedish isolate of PCV-2. Veterinary Record 2002; 150: 255-256.
18. Allan GM, McNeilly F, McNair I, Meehan B, Marshall B, Ellis J, Lasagna C, Boriosi G, Krakowka S, Reynaud G, Boeuf-Tedeschi L, Bublot N and Charreyre C. Passive transfer of maternal antibodies to PCV2 protects against development of post-weaning multisystemic wasting syndrome (PMWS) experimental infections and a field study. Pig Journal 50:59-67.
19. Allan G, McNeilly F, Meehan B, McNair I, Ellis J, Krakowka S, Fossum C, Wattrang E, Wallgren P, Adair B. Reproduction of postweaning multisystemic wasting syndrome in pigs experimentally inoculated with a Swedish porcine circovirus 2 isolate. Journal of Veterinary Diagnostic Investigation 2003; 15(6):553-560.
20. Baekbo P, Hassing AG, Olsen P, Lorenzen B, Lauridsen C. Vitamin E status of the weaned pig as a riskfactor for dying of PMWS. Proceedings of the 4th International Symposium on Emerging and Re-emerging Pig Diseases. PRRS, PMWS, Swine Influenza, Rome 2003: 220-221.
21. Balasch M, Segalés J, Rosell C, Domingo M, Mankertz A, Urniza A and Plana-Durán J. Experimental inoculation of conventional pigs with tissue homogenates from pigs with post-weaning multisystemic wasting syndrome. Journal of Comparative Pathology 1999; 121:139-148.
22. Beattie, V.E., Burrows, M.S., Moss, B.W., Weatherup, R.N. The effect of food deprivation prior to slaughter on performance, behaviour and meat quality. Meat Science 2002; 62: 412-418.
23. Beattie, V.E., Weatherup, R.N., Kilpatrick, D.J. The effect of providing additional feed in a highly accessible trough on feeding behaviour and growth performance of weaned pigs. Irish Journal of Agricultural and Food Research 1999; 38: 209-216.
24. Beattie, V.E., Weatherup, R.N., Moss, B.W., Walker, N. The effect of increasing carcass weight of finishing boars and gilts on joint composition and meat quality. Meat Science 1999; 52:205-212.
25. Blanchard P, Mahe D, Cariolet R, Truong C, Le Dimna M, Arnauld C, Rose N, Eveno E, Albina E, Madec F, Jestin A. An ORF2 protein-based ELISA for porcine circovirus type 2 antibodies in post-weaning multisystemic wasting syndrome. Veterinary Microbiology 2003; 94(3):183-194.
26. Blanchard P, Mahe D, Cariolet R, Keranflec'h A, Baudouard MA, Cordioli P, Albina E, Jestin A. Protection of swine against post-weaning multisystemic wasting syndrome (PMWS) by porcine circovirus type 2 (PCV2) proteins. Vaccine 2003; 21(31):4565-4575.
27. Brunet S., and Charreyre C. Comparison of sequences of PCV2 strains, Proceedings of the 16th IPVS – Melbourne Australia 2000; 629
28. Bogdan J, West K, Clark E, Konoby C, Haines D, Allan G, McNeilly F, Meehan B, Krakowka S, Ellis JA. Association of porcine circovirus 2 with reproductive failure in pigs: a retrospective study, 1995-1998. Canadian Veterinary Journal 2001; 42(7):548-550.
29. Calsamiglia M, Segales J, Quintana J, Rosell C and Domingo M. Detection of Porcine Circovirus Types 1 and 2 in Serum and Tissue Samples of Pigs with and without Postweaning Multisystemic Wasting Syndrome. Journal of Clinical Microbiology 2002; 40:1848-1850.
30. Carrasco L, Segalés J, Bautista MJ, Gómez-Villamandos JC, Rosell C, Ruiz-Villamor E and Sierra MA. Intestinal chlamydial infection concurrent with postweaning multisystemic wasting syndrome in pigs. Veterinary Record 2000; 146: 21-23.
31. Charreyre C., Boeuf, L., Brunet, S., and Reynaud G. Natural transmission of PCV2 in seronegative 9 week old pigs. Proceedings of the 16th IPVS – Melbourne Australia 2000; 574
32. Charreyre C., Boeuf, L., Brunet S., and Reynaud G. No evidence of reactivation of PCV2 at farrowing time. Proceedings of the 16th IPVS – Melbourne Australia 2000; 628
33. Charreyre C., Boeuf, L., and Reynaud G. Natural decrease of anti-PCV2 maternal antibodies in conventional piglets. Proceedings of the 16th IPVS – Melbourne Australia 2000; 630
34. Charreyre C., Boeuf-Tedeschi L., Bublot, M., and Reynaud G. Virus neutralising ability of anti-PCV2 antibody responses. International Conference on ssDNA viruses of Plants, Birds, Pigs and Primates – St-Malo France 2001
35. Charreyre C., Bésème S., Boeuf-Tedeschi, L., Bublot, M., and Reynaud G., Protection against PCV2 exeprimental challenge in 3 week-old piglets by maternal antibodies. Proceedings of the 17th IPVS – Ames IO, USA 2002;
36. Charreyre C., Bésème S., Boeuf-Tedeschi, L., Bublot, M., and Reynaud G., Serological profiles of pigs with and without experimental PMWS. Proceedings of the 17th IPVS – Ames IO, USA 2002;
37. Charreyre C., PMWS- Immunological stimulation and clinical signs. Proceedings of the 11th Swine Disease Conference for Swine Practicioners, Ames IO, USA 2003;161-169
38. Chianini F, Majó N, Segalés J, Domínguez J and Domingo M. Immunohistochemical characterisation of PCV2 associate lesions in lymphoid and non-lymphoid tissues of pigs with natural postweaning multisystemic wasting syndrome (PMWS). Veterinary Immunology and Immunopathology 2003; 94(1-2):63-75.
39. Darwich L, Segalés J, Domingo M and 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. Clinical Diagnostic Laboratory Immunology 2002; 9: 236-242.
40. Darwich L, Pie S, Rovira A, Segales J, Domingo M, Oswald IP, Mateu E. Cytokine mRNA expression profiles in lymphoid tissues of pigs naturally affected by postweaning multisystemic wasting syndrome. Journal of General Virology 2003 ; 84(Pt 8):2117-2125.
41. Darwich L, Balasch M, Plana-Duran J, Segales J, Domingo M, Mateu E. Cytokine profiles of peripheral blood mononuclear cells from pigs with postweaning multisystemic wasting syndrome in response to mitogen, superantigen or recall viral antigens. Journal of General Virology 2003; 84(Pt 12):3453-3457.
42. Ellis J, Hassard L, Clark E, Harding J, Allan G, Willson P, Strokappe J, Martin K, McNeilly F, Meehan B, Todd D, Haines D. Isolation of circovirus from lesions of pigs with postweaning multisystemic wasting syndrome. Canadian Veterinary Journal 1998; 39(1):44-51.
43. Ellis JA, Krakowa S, Allan G, Clark E, Kennedy S. "The clinical scope of porcine reproductive and respiratory syndrome virus infection has expanded since 1987": an alternative perspective. Veterinary Pathology 1999; 36(3):262-265.
44. Ellis J, Krakowka S, Lairmore M, Haines D, Bratanich A, Clark E, Allan G, Konoby C, Hassard L, Meehan B, Martin K, Harding J, Kennedy S and McNeilly F. Reproduction of lesions of postweaning multisystemic wasting syndrome in gnotobiotic piglets. Journal of Veterinary Diagnostic Investigation 1999; 11: 3-14.
45. Ellis JA, Bratanich A, Clark EG, Allan G, Meehan B, Haines DM, Harding J, West KH, Krakowka S, Konoby C, Hassard L, Martin K and McNeilly F. Coinfection by porcine circoviruses and porcine parvovirus in pigs with naturally acquired postweaning multisystemic wasting syndrome. Journal of Veterinary Diagnostic Investigation 2000; 12: 21-27.
46. Ellis JA, Wiseman BM, Allan G, Konoby C, Krakowka S, Meehan BM, McNeilly F. Analysis of seroconversion to porcine circovirus 2 among veterinarians from the United States and Canada. Journal of the American Veterinary Medical Association 2000; 217(11):1645-1646.
47. Ellis JA, Konoby C, West KH, Allan GM, Krakowka S, McNeilly F, Meehan B, Walker I. Lack of antibodies to porcine circovirus type 2 virus in beef and dairy cattle and horses in western Canada. Canadian Veterinary Journal 2001; 42(6):461-464.
48. Ellis J, Spinato M, Yong C, West K, McNeilly F, Meehan B, Kennedy S, Clark E, Krakowka S, Allan G. Porcine circovirus 2-associated disease in Eurasian wild boar. Journal of Veterinary Diagnostic Investigation 2003 ; 15(4):364-368.
49. Gilpin DF, McCullough K, Meehan BM, McNeilly F, McNair I, Stevenson LS, Foster JC, Ellis JA, Krakowka S, Adair BM, Allan GM. In vitro studies on the infection and replication of porcine circovirus type 2 in cells of the porcine immune system. Veterinary Immunology and Immunopathology 2003; 94(3-4):149-161.
50. Harding JC. Post-weaning multisystemic wasting syndrome: preliminary epidemiology and clinical findings. Proceedings of the Western Canadian Association of Swine Practitioners, 1996; p21.
51. Harding JCS and Clark EG. Recognizing and diagnosing postweaning multisystemic wasting syndrome (PMWS). Journal of Swine Health and Production 1997; 5: 201-203.
52. Hassing AG, Botner A, Ladekjaer-Mikkelsen AS, Baekbo P, Jorsal SE, Bille-Hansen V. Postweaning multisystemic wasting syndrome in Denmark. Proceeding of the 17th International Pig Veterinary Society 2002: p173.
53. Hassing AG, Botner A, Ladekjaer-Mikkelsen AS, Kristensen CS, Jorsal SE, Bille-Hansen V, Baekbo P. Characterisation of the first cases of PMWS in Denmark. Proceedings of the 4th International Symposium on Emerging and Re-emerging Pig Diseases. PRRS, PMWS, Swine Influenza, Rome 2003: 211-212.
54. Hassing AG, Kristensen CS, Baekbo P. Effect of sow on the mortality of pigs after weaning. Proceedings of the 4th International Symposium on Emerging and Re-emerging Pig Diseases. PRRS, PMWS, Swine Influenza, Rome 2003: 193.
55. Hasslung FC, Berg M, Allan GM, Meehan BM, McNeilly F, Fossum C. Identification of a sequence from the genome of porcine circovirus type 2 with an inhibitory effect on IFN-alpha production by porcine PBMCs. Journal of General Virology 2003; 84(Pt 11):2937-45.
56. Kennedy S, Allan G, McNeilly F, Adair BM, Hughes A, Spillane P. Porcine circovirus infection in Northern Ireland. Veterinary Record 1998; 142(18):495-496.
57. Kennedy S, Moffett D, McNeilly F, Meehan B, Ellis J, Krakowka S and 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. Journal of Comparative Pathology 2000; 122: 9-24.
58. Kennedy S, Meehan B, McNeilly F, Ellis J, Krakowka S, Allan G. Postweaning multisystemic wasting syndrome: experimental studies with porcine circovirus type 2. In: Zimmerman JJ, Yoon KJ, Morilla A (Ed), Trends in Emerging Viral Diseases of Swine, Iowa State University Press, 2002. pp305-307.
59. Kennedy S, Segales J, Rovira A, Scholes S, Domingo M, Moffett D, Meehan B, O'Neill R, McNeilly F, Allan G. Absence of evidence of porcine circovirus infection in piglets with congenital tremors. Journal of Veterinary Diagnostic Investigation 2003; 15(2):151-156.
60. Krakowka S, Ellis JA, Meehan B, Kennedy S, McNeilly F and Allan G. Viral wasting syndrome of swine: experimental reproduction of postweaning multisystemic wasting syndrome in gnotobiotic swine by coinfection with porcine circovirus 2 and porcine parvovirus. Veterinary Pathology 2000; 37: 254-263.
61. Krakowka S, Ellis JA, McNeilly F, Ringler S, Rings DM and Allan G. Activation of the immune system is the pivotal event in the production of wasting disease in pigs infected with porcine circovirus-2 (PCV-2). Veterinary Pathology 2001; 38: 31-42.
62. Krakowka S, Ellis JA, McNeilly F, Gilpin D, Meehan B, McCullough K, Allan G. Immunologic features of porcine circovirus type 2 infection. Viral Immunology 2002; 15(4):567-82.
63. Kyriakis SC, Saoulidis K, Lekkas S, Miliotis CC, Papoutsis PA and Kennedy S. The effects of immuno-modulation on the clinical and pathological expression of postweaning multisystemic wasting syndrome. Journal of Comparative Pathology 2002; 126: 38-46.
64. Labarque GG, Nauwynck HJ, Mesu AP, Pensaert MB. Seroprevalence of porcine circovirus types 1 and 2 in the Belgian pig population. Veterinary Quarterly 2000; 22(4):234-236.
65. Ladekjaer-Mikkelsen AS, Nielsen J, Storgaard T, Botner A, Allan G and McNeilly F. Transplacental infection with PCV-2 associated with reproductive failure in a gilt. Veterinary Record 2001; 148: 759-760.