First virological and pathological study of Göttingen Minipigs with Dippity Pig Syndrome (DPS)

Abstract

Dippity Pig Syndrome (DPS) is a well-known but rare complex of clinical signs affecting minipigs, which has not been thoroughly investigated yet. Clinically affected animals show acute appearance of red, exudating lesions across the spine. The lesions are painful, evidenced by arching of the back (dipping), and the onset of clinical symptoms is generally sudden. In order to understand the pathogenesis, histological and virological investigations were performed in affected and unaffected Göttingen Minipigs (GöMPs). The following DNA viruses were screened for using PCR-based methods: Porcine cytomegalovirus (PCMV), which is a porcine roseolovirus (PCMV/PRV), porcine lymphotropic herpesviruses (PLHV-1, PLHV-2, PLHV-3), porcine circoviruses (PCV1, PCV2, PCV3, PCV4), porcine parvovirus 1 (PPV1), and Torque Teno sus virus (TTSuV1, TTSuV2). Screening was also performed for integrated porcine endogenous retroviruses (PERV-A, PERV-B, PERV-C) and recombinant PERV-A/C and their expression as well as for the RNA viruses hepatitis E virus (HEV) and SARS-CoV-2. Eight clinically affected and one unaffected GöMPs were analyzed. Additional unaffected minipigs had been analyzed in the past. The analyzed GöMPs contained PERV-A and PERV-B integrated in the genome, which are present in all pigs and PERV-C, which is present in most, but not all pigs. In one affected GöMPs recombinant PERV-A/C was detected in blood. In this animal a very high expression of PERV mRNA was observed. PCMV/PRV was found in three affected animals, PCV1 was found in three animals with DPS and in the healthy minipig, and PCV3 was detected in two animals with DPS and in the unaffected minipig. Most importantly, in one animal only PLHV-3 was detected. It was found in the affected and unaffected skin, and in other organs. Unfortunately, PLHV-3 could not be studied in all other affected minipigs. None of the other viruses were detected and using electron microscopy, no virus particles were found in the affected skin. This data identified some virus infections in GöMPs with DPS and assign a special role to PLHV-3. Since PCMV/PRV, PCV1, PCV3 and PLHV-3 were also found in unaffected animals, a multifactorial cause of DPS is suggested. However, elimination of the viruses from GöMPs may prevent DPS.

Limited availability of methods for the detection of xenotransplantation‐relevant viruses in veterinary laboratories

“…For the first time, synthetic gene blocks containing partial sequences of several viruses were used as a positive control 34 . In an extended study analyzing Göttingen minipigs diseased with the dippity pig syndrome as model, 15 viruses were tested including PERV‐A/C 35 (Table 3, screening pig population 3, SSP3). The methods worked and detected PCMV/PRV, PCV1, PCV3, PLHV‐3, and PERV‐A/C in one or more animals.…”

“…SPP3, screening pig population 3, screening Göttingen minipigs with dippity pig syndrome, dark grey 35 …”

Emergence of novel circoviruses in humans and pigs and their possible importance for xenotransplantation and blood transfusions

“…38 Interestingly, it has also been Greek pig 39 and dippity pig syndrome in Göttingen minipigs. 40 It should be mentioned that PCV3 can be found in invertebrates, in ticks and mosquitoes 41,42 which could indicate that these species may serve as a potential transmission vector in the life-cycle of PCV3.…”

“…PCV3 can be found in most pigs on a global basis including wild boars and domestic pigs with or without clinical signs and are often associated with various other coinfections 38 . Interestingly, it has also been associated with unusual syndromes including erythema multiform in a Greek pig 39 and dippity pig syndrome in Göttingen minipigs 40 . It should be mentioned that PCV3 can be found in invertebrates, in ticks and mosquitoes 41,42 which could indicate that these species may serve as a potential transmission vector in the life‐cycle of PCV3.…”

Prevalence of antibodies against adeno-associated viruses (AAVs) in Göttingen Minipigs: Implications for Gene Therapy and Xenotransplantation

“…Therefore, these animals were carefully screened for different xenotransplantation-relevant viruses [17][18][19][20][21][22][23]. AAV were not screened until now in Göttingen Minipigs, and they are not included into the list of viruses "not permitted in swine with designated pathogen-free status" to be used in xenotransplantation published by Fishman [24].…”