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.
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
Yuri
Y
Martina
Sunil
S
Kurian
Stephanie
S
Cherqui
Gabriel
G
Evanoff
Carolyn
C
Wilson
Daniel R
DR
Salomon
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