Abstract
Pig to human xenotransplantation is considered to be a possible approach to alleviate the shortage of human allografts. Porcine endogenous retrovirus (PERV) is the most significant pathogen in xenotransplantation. We screened for pigs that consistently did not transmit human-tropic replication competent PERVs (HTRC PERVs), namely, non-transmitting pigs. Then, we conducted whole-genome resequencing and full-length transcriptome sequencing to further investigate the sequence characteristics of one non-transmitting pig. Using in vitro transmission assays, we found 5 (out of 105) pigs of the Chinese Wuzhishan minipig inbred line that did not transmit PERV to human cells, i.e., non-transmitting pigs. Whole-genome resequencing and full-length transcriptome sequencing of one non-transmitting pig showed that all of the pol genes were defective at both the genome and transcript levels. We speculate that the defective PERV pol genes in this pig might be attributable to the long-term inbreeding process. This discovery is promising for the development of a strain of highly homozygous and genetically stable pigs with defective PERV pol genes as a source animal species for xenotransplantation.
Highlights
Pigs are considered to be the most suitable donor animals for xenotransplantation because of their anatomical and physiological similarities to humans, large litter size, short gestation period and genetic malleability [1]
The pigs studied in this study were from a highly inbred strain of Chinese Wuzhishan minipigs (WZSPs), which was developed by the Institute of Animal Science of the Chinese Academy of Agriculture Science (CAAS) based on the inbreeding of one male and one female WZSP by full-sib mating over more than 24 generations
We conducted in vitro transmission assays to screen for WZSPs that did not transmit Porcine endogenous retrovirus (PERV) from pig to human cells
Summary
Pigs are considered to be the most suitable donor animals for xenotransplantation because of their anatomical and physiological similarities to humans, large litter size, short gestation period and genetic malleability [1]. Porcine endogenous retroviruses (PERVs) cannot be eliminated in this way since they are integrated into the genomes of all pigs [2]. Transspecies transmission has been shown for many retroviruses, including human immunodeficiency virus type 1 and 2 (HIV-1/2), human T-cell lymphotropic virus type 1 and 2 (HTLV-1/2), Koala retrovirus (KoRV) and Gibbon ape leukemia virus (GALV), and these viruses can cause more serious disease in newly infected hosts than in their natural hosts [4–8]. Transmission of PERVs has not been observed when animals (including nonhuman primates) were inoculated with PERV preparations, during preclinical xenotransplantation or in clinical transplantation to humans [9, 10], PERVs share the pathogenic potential and features common to other retroviruses and remain a major potential zoonotic risk in xenotransplantation
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