Pseudotyping of porcine endogenous retrovirus by xenotropic murine leukemia virus in a pig islet xenotransplantation model

Am J Transplant. 2005 Aug;5(8):1837-47. doi: 10.1111/j.1600-6143.2005.00978.x.

Abstract

The potential of porcine endogenous retrovirus (PERV) as a human pathogen, particularly as a public health risk, is a major concern for xenotransplantation. In vitroPERV transmission to human cells is well established. Evidence from human/pig hematopoietic chimeras in immunodeficient mice suggests PERV transmission from pig to human cells in vivo. However, recently Yang et al. demonstrated in such a model that PERV-C, a nonhuman-tropic class, could be transmitted via pseudotyping by xenotropic murine leukemia virus (X-MLV). We developed a mouse pig islet xenotransplant model, where pig and human cells are located in physically separate compartments, to directly assess PERV transmission from a functional pig xenograft. X-MLV efficiently pseudotypes all three classes of PERV, including PERV-A and -B that are known to productively infect human cell lines and PERV-C that is normally not infectious for human cells. Pseudotyping also extends PERV's natural tropism to nonpermissive, nonhuman primate cells. X-MLV is activated locally by the surgical procedure involved in the tissue transplants. Thus, the presence and activation of endogenous X-MLV in immunodeficient mice limits the clinical significance of previous reports of in vivo PERV transmission from pig tissues to human cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • DNA, Viral / isolation & purification*
  • Endogenous Retroviruses / genetics*
  • Endogenous Retroviruses / isolation & purification
  • Humans
  • Islets of Langerhans / virology*
  • Islets of Langerhans Transplantation / immunology*
  • Leukemia Virus, Murine / physiology*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Models, Animal
  • Molecular Sequence Data
  • Retroviridae Infections / transmission*
  • Retroviridae Infections / virology
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Swine / virology
  • Transplantation Chimera / virology
  • Transplantation, Heterologous*
  • Virus Integration

Substances

  • DNA, Viral