Objective: Porcine endogenous retroviruses (PERVs) pose a risk for xenotransplantations using pig materials as they are present in the genome of all pigs and are able to infect human cells in vitro. Until recently, transmission of PERVs in vivo was only described in severe combined immunodeficient (SCID) and nude mice inoculated with PERV-producing cells. However, in this series of experiments microchimerism could not be excluded. To overcome this problem, the risk of PERV infection was addressed in a similar way but using cell-free inoculation of mouse cells in vitro and SCID mice in vivo. Methods: Mouse cell lines and primary cells were incubated in vitro with PERV-A, with a recombinant PERV-A/C and with PERV-B. Provirus integration was assessed by PCR. Reverse transcriptase activity was measured in the cell supernatants. SCID mice were inoculated in vivo with cell-free virus at high titers. Results: None of the mouse cell lines and primary cells could be infected by PERV and no provirus integration was observed in different organs of the inoculated SCID mice. Conclusion: The data indicate that PERV-A, PERV-A/C and PERV-B could not infect different mouse cells. These data correlate with the recent finding that mouse cells lack a functional receptor for PERV-A. Although the receptor for PERV-B is still unknown, these data suggest that previously reported PERV transmissions to SCID and nude mice in vivo might be due to microchimerism or pseudotyping with murine viruses and indicate that normal mice are an inappropriate model for the study of PERV infection and pathogenesis.

Keywords:
Xenotransplantation, Porcine endogenous retroviruses, Host range, Animal model
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© 2005 S. Karger AG, Basel
2005
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