1887

Abstract

Using transgenic pigs as the source of cells or organs for xenotransplantation is associated with the risk of porcine endogenous retrovirus (PERV) transmission. Multiple proviruses are integrated into the genome of all pigs, and virus particles, some of which are able to infect human cells, are released from normal pig cells. In order to evaluate the potential risk posed by the transmission of PERVs, infection studies were performed as a basis for small animal as well as non-human primate models. infectivity was demonstrated for permanent cell lines and primary cells from a wide range of species. Productive infection was shown using reverse transcriptase (RT) assays and RT–PCR for mink, feline and human kidney cell lines, primary rhesus peripheral blood mononuclear cells (PBMCs), and baboon spleen cells and PBMCs as well as for different human lymphoid and monocyte cell lines and PBMCs. In an attempt to establish a small animal model, naive guinea pigs, non-immunosuppressed rats, rats immunosuppressed by cyclosporin-A and immunosuppressed rats treated with cobra venom factor were inoculated with PERVs produced from porcine kidney PK-15 cells, infected human 293 kidney cells and mitogen-stimulated porcine PBMCs. Animals were also inoculated with PERV-producing PK-15 and 293 cells. No antibodies against PERV and no provirus integration were observed in any of the treated animals. This suggests that productive infection of these animals did not occur in this experimental setting.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-82-4-837
2001-04-01
2019-10-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/82/4/0820837a.html?itemId=/content/journal/jgv/10.1099/0022-1317-82-4-837&mimeType=html&fmt=ahah

References

  1. Akiyoshi, D. E., Denaro, M., Zhu, H., Greenstein, J. L., Banerjee, P. & Fishman, J. A. ( 1998; ). Identification of a full-length cDNA for an endogenous retrovirus of miniature swine. Journal of Virology 72, 4503-4507.
    [Google Scholar]
  2. Argirova, R. M., Zakharova, L. G. & Altstein, A. D. ( 1973; ). The sensitivity of embryonal cell cultures from rats and mice of different lines: the transformation-destructive effect of mouse sarcoma virus. Voprosy Virusologii 18, 54–59 (in Russian).
    [Google Scholar]
  3. Armstrong, J. A., Porterfield, J. S. & De Madrid, A. T. ( 1971; ). C-type virus particles in pig kidney cell lines. Journal of General Virology 10, 195-198.[CrossRef]
    [Google Scholar]
  4. Bouillant, A. M. P., Greig, A. S., Lieber, M. M. & Todaro, G. J. ( 1975; ). Type C virus production by a continuous line of pig oviduct cells (PFT). Journal of General Virology 27, 173-180.[CrossRef]
    [Google Scholar]
  5. Breese, S. S.Jr ( 1970; ). Virus-like particles occurring in cultures of stable pig kidney cell lines. Archiv für die Gesamte Virusforschung 30, 401-404.[CrossRef]
    [Google Scholar]
  6. Czauderna, F., Fischer, N., Boller, K., Kurth, R. & Tönjes, R. ( 2000; ). Establishment and characterization of molecular clones of porcine endogenous retroviruses replicating on human cells. Journal of Virology 74, 4028-4038.[CrossRef]
    [Google Scholar]
  7. Deng, Y. M., Tuch, B. E. & Rawlinson, W. D. ( 2000; ). Transmission of porcine endogenous retroviruses in severe combined immunodeficient mice xenotransplanted with fetal porcine pancreatic cells. Transplantation 70, 1010-1016.[CrossRef]
    [Google Scholar]
  8. Denner, J. ( 1998; ). Immunosuppression by retroviruses: implications for xenotransplantation. Annals of the New York Academy of Sciences 862, 75-86.[CrossRef]
    [Google Scholar]
  9. Denner, J. ( 1999; ). Immunsuppression durch Retroviren: Implikationen für die Xenotransplantation. Transplantationsmedizin 11, 223-233.
    [Google Scholar]
  10. Fan, H. ( 1994; ). Retroviruses and their role in cancer. In The Retroviridae , pp. 313-362. Edited by J. A. Levy. New York:Plenum Press.
  11. Frazier, M. E. ( 1985; ). Evidence for retrovirus in miniature swine with radiation-induced leukemia or metaplasia. Archives of Virology 83, 83-97.[CrossRef]
    [Google Scholar]
  12. Freshney, R. I. (1987). Culture of Animal Cells. A Manual of Basic Technique. New York: John Wiley.
  13. Gazzolo, L., Smicovic, D. & Martin-Berthelon, M. C. ( 1971; ). The presence of C-type RNA virus particles in a rat embryo cell line spontaneously transformed in tissue culture. Journal of General Virology 12, 303-311.[CrossRef]
    [Google Scholar]
  14. Hardy, W. D. ( 1993; ). Feline oncoretroviruses. In The Retroviridae , pp. 109-180. Edited by J. A. Levy. New York:Plenum Press.
  15. Kindig, D. A. & Kirsten, W. H. ( 1967; ). Virus-like particles in established cell lines: electron microscopic observations. Science 155, 1543-1545.[CrossRef]
    [Google Scholar]
  16. Le Tissier, P. l., Stoye, J. P., Takeuchi, Y., Patience, C. & Weiss, R. A. ( 1997; ). Two sets of human-topic pig retrovirus. Nature 389, 681-682.[CrossRef]
    [Google Scholar]
  17. Lieber, M. M., Beneviste, R. E., Livingston, D. M. & Todaro, G. J. ( 1973; ). Mammalian cells in culture frequently release type C viruses. Science 182, 56-59.[CrossRef]
    [Google Scholar]
  18. Lieber, M. M., Sherr, C. J., Benveniste, R. E. & Todaro, G. J. ( 1975; ). Biologic and immunologic properties of porcine type C viruses. Virology 66, 616-619.[CrossRef]
    [Google Scholar]
  19. Luft, J. H. ( 1961; ). Improvements in epoxy resin embedding methods. Journal of Biophysical and Biochemical Cytology 9, 409-413.[CrossRef]
    [Google Scholar]
  20. Martin, U., Kiessig, V., Blusch, J. H., Haverich, A., von der Helm, K., Herden, T. & Steinhoff, G. ( 1998; ). Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells. Lancet 352, 692-694.[CrossRef]
    [Google Scholar]
  21. Paradis, K., Langford, G., Long, Z., Heneine, W., Sandstrom, P., Switzer, W. M., Chapman, L. E., Lockey, C., Onions, D. & Otto, E. ( 1999; ). Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. Science 285, 1236-1241.[CrossRef]
    [Google Scholar]
  22. Patience, C., Takeuchi, Y. & Weiss, R. A. ( 1997; ). Infection of human cells by an endogenous retrovirus of pigs. Nature Medicine 3, 282-286.[CrossRef]
    [Google Scholar]
  23. Porter, C. D., Lukacs, K. V., Box, G., Takeuchi, Y. & Collins, M. K. ( 1998; ). Cationic liposomes enhance the rate of transduction by recombinant retroviral vector in vitro and in vivo. Journal of Virology 72, 4832-4840.
    [Google Scholar]
  24. Seitz, B., Baktanian, E., Gordon, E. M., Anderson, W. F., LaBree, L. & McDonnell, P. J. ( 1998; ). Retroviral vector-mediated gene transfer into keratocytes: in vitro effects of polybrene and protamine sulfate. Graefe’s Archive for Clinical and Experimental Ophthalmology 23, 602-612.
    [Google Scholar]
  25. Starzl, T. E., Fung, J., Tzakis, A., Todo, S., Demetris, A. J., Marino, I. R., Doyle, H., Zeevi, A., Warty, V. & Michaels, M. ( 1993; ). Baboon-to-human liver transplantation. Lancet 341, 65-71.[CrossRef]
    [Google Scholar]
  26. Swindle, M. M. ( 1998; ). Defining appropriate health status and management programs for specific-pathogen-free swine for xenotransplantation. Annals of the New York Academy of Sciences 862, 111-120.[CrossRef]
    [Google Scholar]
  27. Tacke, S. J., Kurth, R. & Denner, J. ( 2000a; ). Porcine endogenous retroviruses inhibit human immune cell function: risk for xenotransplantation? Virology 268, 87-93.[CrossRef]
    [Google Scholar]
  28. Tacke, S. J., Specke, V., Stephan, O., Seibold, E., Bodusch, K. & Denner, J. ( 2000b; ). Porcine endogenous retroviruses: diagnostic assays and evidence for immunosuppressive properties. Transplantation Proceedings 32, 1166.[CrossRef]
    [Google Scholar]
  29. Takeuchi, Y., Cosset, F.-L., Lachmann, P. J., Okada, H., Weiss, R. A. & Collins, M. K. L. ( 1994; ). Type C retrovirus inactivation by human complement is determined by both the viral genome and the producer cell. Journal of Virology 68, 8001-8007.
    [Google Scholar]
  30. Takeuchi, Y., Porter, C. D., Strahan, K. M., Preece, A. F., Gustafsson, K., Cosset, F.-L., Weiss, R. A. & Collins, M. K. L. ( 1996; ). Sensitization of cells and retroviruses to human serum by (α1–3)galactosyltransferase. Nature 379, 85-88.[CrossRef]
    [Google Scholar]
  31. Takeuchi, Y., Patience, C., Magre, S., Weiss, R. A., Banerjee, P. T., Le Tissier, P. & Stoye, J. P. ( 1998; ). Host range and interference studies of three classes of pig endogenous retrovirus. Journal of Virology 72, 9986-9991.
    [Google Scholar]
  32. Themis, M., Forbes, S. J., Chan, L., Cooper, R. G., Etheridge, C. J., Miller, A. D., Hodgson, H. J. & Coutelle, C. ( 1998; ). Enhanced in vitro and in vivo gene delivery using cationic agent complexed retrovirus vectors. Gene Therapy 5, 1180-1186.[CrossRef]
    [Google Scholar]
  33. Todaro, G. J., Benveniste, R. E., Lieber, M. M. & Sherr, C. J. ( 1974; ). Characterization of a type C virus released from the porcine cell line PK(15). Virology 58, 65-74.[CrossRef]
    [Google Scholar]
  34. van der Laan, L. J. W., Lockely, C., Griffeth, B. C., Fraiser, F. S., Wilson, C. A., Onions, D. E., Hering, J., Long, Z., Otto, E., Torbett, B. E. & Salomon, D. R. ( 2000; ). Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice. Nature 407, 501-504.
    [Google Scholar]
  35. Wilson, C. A., Wong, S., Muller, J., Davidson, C. E., Rose, T. M. & Burd, P. ( 1998; ). Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells. Journal of Virology 72, 3082-3087.
    [Google Scholar]
  36. Wilson, C. A., Wong, S., VanBrocklin, M. & Federspiel, J. ( 2000; ). Extended analysis of the in vitro tropism of porcine endogenous retrovirus. Journal of Virology 74, 49-56.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-82-4-837
Loading
/content/journal/jgv/10.1099/0022-1317-82-4-837
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error