September 2004
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Journal of Clinical Investigation
Pig-human transplantation not PERVertedMouse retrovirus mediates porcine endogenous retrovirus transmission into human cells in long-term human-porcine chimeric miceOrgan or tissue transplantation is a potentially life-saving measure for millions of individuals who have suffered organ failure or require tissue grafts for a variety of reasons. Today thousands die while waiting for suitable organs or tissues to become available. One potential means for relieving this shortage has been through xenotransplantation, that is to use organs or tissues from other organisms, such as pigs.
A major concern of xenotransplantation is the possibility of transmitting pathogens from these other species into the donor. Particular attention, for the case of transplantation of tissues and organs from pigs, has been paid to a set of pig-derived viruses called PERVs (for Porcine Endogenous RetroViruses) because they possess the ability, though limited, to replicate in human cells. So far, the actually frequency of PERV transmission within a living organism has not been tested in either patients or animal models under circumstances where human cells are exposed over a long term to similar amount of pig tissue.
Yong-Guang Yang and colleagues, from Massachusetts General Hospital/Harvard Medical School, provide new data that indicate the dangers of such viral transmission may be extremely low and that pigs may be a safer source of transplantation material than previously thought. To carry out their assessment, the researchers developed a new xenotransplantation model where human cells coexist with large numbers of porcine cells in a transgenic mouse.
The study showed that these cells could in fact coexist long-term without PERV infection in the human cells. Although, the authors did find that human cells in these mice did contain PERV sequences, further investigation proved that this was the result of a mouse retrovirus infecting the pig cells and then transmitting the PERV from there to the human cells. This is not a concern in actual xenotransplantation, but intriguingly may account for previous observations of PERV transmission into human cells in other mouse studies, and indicates the importance of developing robust models that do not contain additional replication capable viruses.
Given the absence of direct human cell transmission of PERV, these work supports the potential safety of using pigs as source animals for transplantation to humans.
TITLE: Mouse retrovirus mediates porcine endogenous retrovirus transmission into human cells in long-term human-porcine chimeric mice
AUTHOR CONTACT:
Yong-Guang Yang
Massachusetts General Hospital/Harvard Medical School, 13th Street, Boston, MA 02129, USA Phone: 617-726-6959; Fax: 617-724-9892; E-mail: yongguang.yang@tbrc.mgh.harvard.edu
View the PDF of this article at: http://www.jci.org/cgi/content/full/114/5/695
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