Early weaning completely eliminates porcine cytomegalovirus from a newly established pig donor facility for xenotransplantation

Abstract

For clinical xenotransplantation, transplants must be free of porcine cytomegalovirus (PCMV). Piglets become infected primarily in the perinatal period by the mother sow. While individual donor animals can be protected from infection by isolation husbandry, success is not guaranteed and this strategy poses the risk of undetected infections and raises animal welfare questions. Here, we present the establishment of a completely PCMV-negative pig herd for breeding donor animals for xenotransplantation. Eleven pregnant DanAvl Basic hybrid sows were purchased from a designated pathogen-free (DPF), PCMV-positive colony and transferred to a new pig facility at the Centre for Innovative Medical Models (CiMM) 4 weeks prior to farrowing. At the age of 24 hours, piglets were early-weaned and transferred to a commercially available Rescue Deck system dedicated to motherless rearing of piglets. Sows were removed from the facility. The PCMV status of F1-generation animals was determined at regular intervals over a period of 14 months by a sensitive real-time PCR-based detection method testing blood, nasal swabs and cultured peripheral blood mononuclear cells (PBMCs). F1 sows were used as recipients of genetically modified embryos to generate a xenotransplant donor herd. Offspring were tested for PCMV accordingly. All offspring have remained PCMV negative over the whole observation period of 14 months. A completely PCMV-negative pig herd for xenotransplantation has thus been successfully established.

Impact of porcine cytomegalovirus on long-term orthotopic cardiac xenotransplant survival

“…In order to prevent transmission of porcine viruses after xenotransplantation, elimination programs had been proposed which are based on selection and isolation of virusnegative animals, vaccination or treatment with an effective antiviral drug (both are not available in the case of PCMV/PRV), early weaning, colostrum deprivation, Caesarean delivery or embryo transfer. Although PCMV/PRV can be transmitted via placenta 53,54 , successful elimination can be achieved by early weaning 35,55 , providing virus-free animals for a safe xenotransplantation.…”

Comparative Analysis of Roseoloviruses in Humans, Pigs, Mice, and Other Species

“…Since there is no effective antiviral drug available [188,189] and no vaccine, prevention of transmission of the virus during xenotransplantation can only be successful by early weaning, colostrum deprivation, Caesarean section, and embryo transfer. PCMV-free pigs were also successfully obtained by early weaning [199][200][201], despite the observation that PCMV/PRV can also be transmitted via the placenta [175,202]. This will lay the foundation for a safe xenotransplantation in near future.…”

“…In pigs, congenital PCMV/PRV infections have been associated with multifocal lesions distributed throughout the cerebrum and cerebellum, and the virus has been isolated from the central nervous system [175]. Now that PCMV/PRV free colonies have been established [199], it would be possible to study the effect of PCMV/PRV in the pig model. Furthermore, transgenic pigs being developed to study Alzheimer's disease should be free of PCMV in order to obtain reliable results.…”

Xenotransplantation literature update, July/August 2018

“…Strategies to eliminate PERV in porcine donor grafts are clarified in the review article by McGregor et al . Later articles in the issue apply methods that have worked to remove risks of infection, such as those used in Munich where Egerer et al produced pigs utterly free of porcine cytomegalovirus. They continue to sustain and breed the pigs naturally for future trials in clinical xenotransplantation.…”