Abstract
Minipigs play an important role in biomedical research and they have also been used as donor animals for preclinical xenotransplantations. Since zoonotic microorganisms including viruses can be transmitted when pig cells, tissues or organs are transplanted, virus safety is an important feature in xenotransplantation. Whereas most porcine viruses can be eliminated from pig herds by different strategies, this is not possible for porcine endogenous retroviruses (PERVs). PERVs are integrated in the genome of pigs and some of them release infectious particles able to infect human cells. Whereas PERV-A and PERV-B are present in all pigs and can infect cells from humans and other species, PERV-C is present in most, but not all pigs and infects only pig cells. Recombinant viruses between PERV-A and PERV-C have been found in some pigs; these recombinants infect human cells and are characterized by high replication rates. PERV-A/C recombinants have been found mainly in minipigs of different origin. The possible reasons of this high prevalence of PERV-A/C in minipigs, including inbreeding and higher numbers and expression of replication-competent PERV-C in these animals, are discussed in this review. Based on these data, it is highly recommended to use only pig donors in clinical xenotransplantation that are negative for PERV-C.
Highlights
IntroductionWorldwide several breeds of minipigs ( called miniature swine or micropigs) have been established (Table 1) and most of these minipigs are used in biomedical research and development, only some of them are favored as pets
Worldwide several breeds of minipigs have been established (Table 1) and most of these minipigs are used in biomedical research and development, only some of them are favored as pets
More than a decade ago, the EU-sponsored RETHINK project has highlighted this use of minipigs in biomedicine, including toxicity testing, which as a consequence adds to the 3Rs of animal testing [15]
Summary
Worldwide several breeds of minipigs ( called miniature swine or micropigs) have been established (Table 1) and most of these minipigs are used in biomedical research and development, only some of them are favored as pets. Sequencing the virus isolated from the mitogen-stimulated PBMCs of the NIH minipig revealed the presence of a recombinant between PERV-A and PERV-C, one breakpoint being in the transmembrane envelope protein, the other upstream to the env [17] Due to this recombination, the backbone PERV-C acquired the receptor binding site of the humantropic PERV-A (Figure 1), which allowed the virus to infect human cells using receptors mentioned above. Pig revealed the presence of a recombinant between PERV-A and PERV-C, one breakpoint being in the transmembrane envelope protein, the other upstream to the env [17] These data confirm the results in other breeds that PERV-A/C is not present in the germ line [31]
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