Mouse retrovirus mediates porcine endogenous retrovirus transmission into human cells in long-term human-porcine chimeric mice

J Clin Invest. 2004 Sep;114(5):695-700. doi: 10.1172/JCI21946.


Porcine endogenous retrovirus (PERV) is a potential pathogen in clinical xenotransplantation; transmission of PERV in vivo has been suggested in murine xenotransplantation models. We analyzed the transmission of PERV to human cells in vivo using a model in which immunodeficient NOD/SCID transgenic mice were transplanted with porcine and human lymphohematopoietic tissues. Our results demonstrate, we believe for the first time, that human and pig cells can coexist long-term (up to 25 weeks) without direct PERV infection of human cells. Despite the transplantation of porcine cells that did not produce human-tropic PERV, human cells from the chimeric mice were frequently found to contain PERV sequences. However, this transmission was due to the pseudotyping of PERV-C (a virus without human tropism) by xenotropic murine leukemia virus, rather than to de novo generation of human-tropic PERV. Thus, pseudotyping might account for the PERV transmission previously observed in mice. The absence of direct human cell infection following long-term in vivo coexistence with large numbers of porcine cells provides encouragement regarding the potential safety of using pigs that do not produce human-tropic PERV as source animals for transplantation to humans.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bone Marrow Transplantation
  • Humans
  • Liver Transplantation
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Molecular Sequence Data
  • Retroviridae / physiology*
  • Retroviridae Infections / transmission*
  • Retroviridae Infections / virology
  • Species Specificity
  • Swine
  • Thymus Gland / transplantation
  • Transplantation Chimera / virology
  • Transplantation, Heterologous*
  • Virus Replication