Corneal Xenotransplantation From Pig to Rhesus Monkey: No Signs of Transmission of Endogenous Porcine Retroviruses

Transplant Proc. 2017 Nov;49(9):2209-2214. doi: 10.1016/j.transproceed.2017.07.018.

Abstract

Background: Xenotransplantations of pig corneas have become an attractive alternative to human corneas. Such xenotransplantations carry the danger, however, of transmission of porcine endogenous retroviruses (PERVs). Here, we investigated whether porcine corneas harbor viral DNA and RNA and whether transplantation to a nonhuman primate would lead to host PERV infection.

Methods: Monkey vein endothelial cells (MVECs) were inoculated with porcine aortic endothelial cell (PAEC) supernatants, and DNA and total RNA of MVECs were tested for PERV by polymerase chain reaction (PCR) and reverse transcription PCR (RT-PCR) assays. Corneas were harvested from Wuzhishan miniature pigs, and the presence of PERV proviral DNA and RNA was analyzed by PCR and RT-PCR, respectively. Fresh or dehydrated corneas were then transplanted to rhesus monkeys, and PERV proviral DNA and RNA were analyzed in host peripheral blood lymphocytes at 6 and 24 months. Furthermore, the presence of PERV sequences was analyzed in the transplant at 24 months.

Results: PCR analysis showed PERV transfection from PAECs to MVECs in vitro. PCR and RT-PCR gave positive signals for PERV subtypes A and B, but not PERV-C, regardless of how the corneas were prepared. No evidence was found for PERV transmission to the host, and the transplant had lost its viral signal at the end of the 24-month period.

Conclusions: Regardless of cornea preparation and storage, PERV transmission from pig to host could not be detected, despite that the transplant was initially PERV-positive. The use of the Wuzhishan miniature pig as the donor may be advantageous because it lacks PERV-C and hence potentially infectious A/C recombinants.

MeSH terms

  • Animals
  • Cornea / virology*
  • Corneal Transplantation / adverse effects
  • Corneal Transplantation / methods*
  • DNA, Viral / analysis
  • Endogenous Retroviruses / genetics*
  • Graft vs Host Disease / virology*
  • Heterografts / virology*
  • Macaca mulatta
  • Polymerase Chain Reaction
  • RNA, Viral / analysis
  • Swine / virology
  • Swine, Miniature
  • Transplantation, Heterologous / adverse effects
  • Transplantation, Heterologous / methods*

Substances

  • DNA, Viral
  • RNA, Viral