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Pseudotyping of Porcine Endogenous Retrovirus by Xenotropic Murine Leukemia Virus in a Pig Islet Xenotransplantation Model
Author(s) -
Martina Yuri,
Kurian Sunil,
Cherqui Stephanie,
Evanoff Gabriel,
Wilson Carolyn,
Salomon Daniel R.
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2005.00978.x
Subject(s) - xenotransplantation , endogenous retrovirus , virology , murine leukemia virus , tropism , biology , transplantation , gammaretrovirus , leukemia , tissue tropism , virus , retrovirus , feline leukemia virus , immunology , medicine , gene , genetics , surgery , genome
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.