Pseudotyping of porcine endogenous retrovirus by xenotropic murine leukemia virus in a pig islet xenotransplantation model.
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.
Martina
Yuri
Y
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
Kurian
Sunil
S
Cherqui
Stephanie
S
Evanoff
Gabriel
G
Wilson
Carolyn
C
Salomon
Daniel R
DR
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004279:DNA, Viral / Q000302:isolation & purification*; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007515:Islets of Langerhans / Q000821:virology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D009052:Leukemia Virus, Murine / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D008969:Molecular Sequence Data; D012192:Retroviridae Infections / Q000635:transmission* / Q000821:virology; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013552:Swine / Q000821:virology; D018183:Transplantation Chimera / Q000821:virology; D014183:Transplantation, Heterologous; D016662:Virus Integration
D004279:DNA, Viral