title: Mouse retrovirus mediates porcine endogenous retrovirus transmission into human cells in long-term human-porcine chimeric mice.
abstract: 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.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. yongguang.yang@tbrc.mgh.harvard.edu
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Yang
authors.forename: James C
authors.initials: JC
authors.lastname: Wood
authors.forename: Ping
authors.initials: P
authors.lastname: Lan
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wilkinson
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
authors.forename: Jay A
authors.initials: JA
authors.lastname: Fishman
authors.forename: Clive
authors.initials: C
authors.lastname: Patience
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016026:Bone Marrow Transplantation; D006801:Humans; D016031:Liver Transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012190:Retroviridae / Q000502:physiology*; D012192:Retroviridae Infections / Q000635:transmission* / Q000821:virology; D013045:Species Specificity; D013552:Swine; D013950:Thymus Gland / Q000637:transplantation; D018183:Transplantation Chimera / Q000821:virology; D014183:Transplantation, Heterologous; D014779:Virus Replication