Abstract
The possible use of pig organs and tissues as xenografts in humans is actively being considered in biomedical research. We therefore examined whether pig endogenous retrovirus (PERV) genomes can be infectiously transmitted to human cells in culture. Two pig kidney cell lines spontaneously produce C-type retrovirus particles. Cell-free retrovirus produced by the PK-15 kidney cell line (PERV-PK) infected pig, mink and human kidney 293 cell lines and co-cultivation of X-irradiated PK-15 cells with human cells resulted in a broader range of human cell infection, including human diploid fibroblasts and B- and T-cell lines. Kidney, heart and spleen tissue obtained from domestic pigs contained multiple copies of integrated PERV genomes and expressed viral RNA. Upon passage in human cells PERV-PK could rescue a Moloney retroviral vector and acquired resistance to lysis by human complement.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Institute of Medicine. Xenotransplantation, science, ethics and public policy. (National Academy Press, Washington DC, 1996).
Nuffield Council on Bioethics. Animal-to-human transplants: The ethics of xeno-transplantation.(London, 1996).
Gunsalus, J.R., Brady, D.A., Coulter, S.M., Gray, B.M., & Edge, A.S.B. Reduction of serum cholesterol in Watanabe rabbits by xenogenic hepato Cellular transplantation. Nature Med. 3, 48–53 (1997).
Starzl, T.E. et al. Baboon-to-human liver transplantation. Lancet 341, 65–71 (1993).
Lehrman, S. AIDS patient given baboon bone marrow. Nature 378, 756 (1995).
Groth, C.G. et al. Transplantation of porcine fetal pancreas to diabetic patients. Lancet 344, 1402–1404 (1994).
Makowa, L. et al The use of a pig liver xenograft for temporary support of a patient with fulminant hepatic failure. Transplantation 59, 1654–1659 (1995).
Ryan, U.S. Complement inhibitory therapeutics and Xenotransplantation. Nature Med. 1, 967–968 (1995).
Bach, F.H. et al. Barriers to Xenotransplantation. Nature Med. 1, 869–873 (1995).
Sandrin, M.S. et al. Enzymatic remodelling of the carbohydrate surface of a xenogenic Cell substantially reduces human antibody binding and complement mediated cytolysis. Nature Med. 1, 1261–1267 (1995).
Foder, W.L. et al. Expression of a human complement inhibitor in a transgenic pig as a model for the prevention of xenogenic hyperacute rejection. Proc. Natl. Acad. Sci. USA 91, 11153–11157 (1994).
McCurry, K.R. et al. Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. Nature Med. 1, 423–427 (1995).
Cozzi, E. & White, D.J.G. The generation of transgenic pigs as potential organ donors for humans. Nature Med. 1, 964–966 (1995).
Stoye, J.P. & Coffin, J.M. The dangers of Xenotransplantation. Nature Med. 1, 1100 (1995).
Allan, J.S. Xenotransplantation at a cross-roads: Prevention versus progress. Nature Med. 2, 18–21 (1996).
Wilkinson, D., Mager, D.L. & Leong, J.A.C. Endogenous human retroviruses. in The Retroviridae (ed. Levy, J. A.). vol. 3, 465–535 (Plenum Press, New York, 1994).
Patience, C. Wilkinson, D.A. & Weiss, R.A. Our retroviral heritage. Trends Genet. (in the press).
Coffin, J.M. Endogenous retroviruses. in RNA Tumor Viruses (eds. Weiss, R.A., Varmus, H.E., Teich, N.M. & Coffin, J.M.). (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1985).
Benveniste, R.E. et al. Infectious type-C virus isolated from baboon placenta. Nature 248, 17–20 (1974).
McAllister, R.M. et al. C-type virus released from cultured human rhabdomyosar-coma Cells. Nature New Biol. 235, 3–6 (1972).
Armstrong, J.A. Porterfield, J.S. & De-Madrid, A.T. C-type virus in pig kidney Cell lines. J. Gen. Virol. 10, 195–198 (1971).
Todaro, G.J., Benveniste, R.E., Lieber, M.M., & Sherr, C.J. Characterisation of a Type C virus released from the porcine Cell line PK (15). Virology 58, 65–74 (1974).
Moennig, V. et al. C-type particles produced by a permanent Cell line from a leukemic pig. II. Physical, chemical, and serological characterization of the particles. Virology 57, 179–188 (1974).
Lieber, M.M., Sherr, C.J., Benveniste, R.E. & Todaro, G.J. Biologic and immuno-logic properties of porcine type C virus. Virology 66, 616–619 (1975).
Takeuchi, Y. et al. Type C retrovirus inactivation by human complement is determined by both the viral genome and the producer Cell. J. Virol. 68, 8001–8007 (1994).
Rother, R.P. et al. A novel mechanism of retrovirus inactivation in human serum mediated by anti-alpha-galactosyl natural antibody. J. Exp. Med. 182, 1345–1355 (1995).
Takeuchi, Y. et al. Sensitization of Cells and retroviruses to human serum by (α1-3) galactosyltransferase. Nature 379, 85–88 (1996).
Tristem, M. et al. Characterisation of a novel murine leukemic virus-related subgroup in mammals. J. Virol. 70, 8241–8246 (1996).
Benveniste, R.E. & Todaro, G.J. Evolution of type C viral genes: Preservation of ancestral murine type C viral sequences in pig Cellular DNA. Proc. Nat. Acad. Sci. USA 72, 4090–4094 (1975).
Levy, J.A. Xenotropic viruses: Murine leukemia viruses associated with NIH Swiss, NZB and other mouse strains. Science 182, 1151–1153 (1973).
Bostock, D.E., & Owen, L.N. Porcine and ovine lymphosarcoma. A review. J. Natl. Cancer Inst. 50, 933–939 (1973).
Kawakami, T.G. et al. C-type virus associated with gibbon lymphosarcoma. Nature New Biol. 235, 170–171 (1972).
Kawakami, T.G., Sun, L., & McDowell, T.S. Natural transmission of gibbon leukemia virus. J. Natl. Cancer Inst. 61, 1113–1115 (1978).
Lieber, M.M. et al. Isolation from the Asian mouse Mus caroli of an endogenous type C virus related to infectious primate type C viruses. Proc. Natl. Acad. Sci. USA 72, 2315–2319 (1975).
Donahue, R.E. et al. Helper virus induced T-Cell lymphoma in non human primates after retroviral mediated gene transfer. J. Exp. Med. 176, 1125–1135 (1992).
Michaels, M.G., & Simmons, R.L. Xenotransplant-associated zoonoses: Strategies for prevention. Transplantation 57, 1–7 (1994).
Scadden, D.T., Fuller, B., & Cunningham, J.M., Human Cells infected with retrovirus vectors acquire an endogenous murine provirus. J. Virol. 64, 424–427 (1990).
Purcell, D.F.J. et al. An array of murine leukemia virus-related elements is transmitted and expressed in a primate recipient of retroviral gene transfer. J. Virol. 70, 887–897 (1996).
Goodchild, N.L., Freeman, J.B., & Mager, D.L., Herv-H endogenous retroviral sequences in human genomic DNA: Evidence for amplification via retrotrans-position. Virology 206, 164–173 (1995).
Patience, C. et al. Human endogenous retrovirus expression and reverse transcrip-tase activity in the T47D mammaiy carcinoma Cell line. J. Virol. 70, 2654–2657 (1996).
Simpson, G.R. et al. Endogenous D-type (HERV-K) related sequences are packaged into retroviral particles in the placenta and possess open reading frames for reverse transcriptase. Virology 222, 451–456 (1996).
Weiss, R.A., Why Cell biologists should be aware of genetically transmitted viruses. Natl. Cancer Inst. Monogr. 48, 183–189 (1978).
Homer. The Odyssey. Translated by E. V. Rieu. Penguin Classics. (1946).
Silver, J., Maudru, T., Fujita, K. & Repaske, R. An RT-PCR assay for the enzyme activity of reverse transcriptase capable of detecting single virions. Nucleic Acids Res. 21, 3593–3594 (1994).
Cosset, F.L., Takeuchi, Y., Battini, J.L., Weiss, R.A. & Collins, M.K. High titer packaging Cells producing recombinant retroviruses resistant to human serum. J. Virol. 69, 7430–7436 (1995).
Tristem, M. Amplification of divergent retroviral elements by PCR. BioTechniques 20, 608–612 (1996).
Simmons, G. et al. Primary syncytium-inducing HIV-1 isolates are dual-tropic and most can use either Lestr or CCR5 as co-receptors for virus entry. J. Virol. 70, 8355–8360 (1996).
Kotani, H. et al. Improved methods of retroviral vector transduction and production for gene therapy. Hum. Cene Ther. 5, 19–28 (1994).
Epstein, M.A., Achong, B.G. & Barr, Y.M. Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Lancet 1, 702–703 (1964).
Achong, B.G., Trumper, P.A., & Giovanella, B.C. C-type virus particles in human tumours transplanted into nude mice. Brit. J. Cancer 34, 203–206 (1976).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Patience, C., Takeuchi, Y. & Weiss, R. Infection of human cells by an endogenous retrovirus of pigs. Nat Med 3, 282–286 (1997). https://doi.org/10.1038/nm0397-282
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/nm0397-282
This article is cited by
-
Monkey survives for two years after gene-edited pig-kidney transplant
Nature (2023)
-
Cardiac Xenotransplantation: a New Frontier for Advanced Heart Failure
Current Treatment Options in Cardiovascular Medicine (2023)
-
Porcine endogenous retrovirus: classification, molecular structure, regulation, function, and potential risk in xenotransplantation
Functional & Integrative Genomics (2023)
-
Design and testing of a humanized porcine donor for xenotransplantation
Nature (2023)
-
Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs
Virology Journal (2022)