Transmission of zoonoses in xenotransplantation: porcine endogenous retroviruses from an immunological and molecular point of view.

BACKGROUND AND OBJECTIVES

Pigs offer an unlimited source of xenografts for humans. The use of transplants from animal origin offers a potential solution to the limited supply of human organs and tissues. However, like many other mammalian species, pigs harbor porcine endogenous retrovirus (PERV), which are encoded in their genomic DNA and are assumed to have been integrated into the porcine germ line more than 7.6 × 106 years ago and showing that the age correlates with the time of separation between pigs and peccaries 7.4 × 106 years ago. The ability of the PERV to infect human cells in vitro has heightened safety concerns regarding the transmission of PERV to pig xenograft recipients. In this study, we detected PERV-AC recombinant virus in porcine genomic DNA that may have resulted from exogenous viral recombination. Infectious risk in xenotransplantation will be defined by the activity of PERV loci in vivo. We identified unique Haemophilus aegyptius III HaeIII gag restriction fragment length polymorphism (RFLP) profiles resulting from single nucleotide polymorphisms; these were found only in animals that produced human tropic PERV.

MATERIALS AND METHODS

Porcine tissues were analyzed using validated assays specific for PERV: polymerase chain reaction (PCR) (for PERV DNA), RT-PCR (for PERV RNA), cell culture, RFLP analysis, and sequence analysis.

CONCLUSIONS AND INTERPRETATION

These findings have demonstrated that the presence of both DNA and RNA forms of porcine endogenous retrovirus in porcine tissues needs to be carefully considered when the infectious disease potential of xenotransplantation is being assessed.