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Science 20 August 1999:
Vol. 285. no. 5431, pp. 1236 - 1241
DOI: 10.1126/science.285.5431.1236
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Research Articles

Search for Cross-Species Transmission of Porcine Endogenous Retrovirus in Patients Treated with Living Pig Tissue

Khazal Paradis, 1* Gillian Langford, 1 Zhifeng Long, 2 Walid Heneine, 3 Paul Sandstrom, 3 William M. Switzer, 3 Louisa E. Chapman, 3 Chris Lockey, 2 David Onions, 4 The XEN 111 Study Group, 5 Edward Otto 2

Pig organs may offer a solution to the shortage of human donor organs for transplantation, but concerns remain about possible cross-species transmission of porcine endogenous retrovirus (PERV). Samples were collected from 160 patients who had been treated with various living pig tissues up to 12 years earlier. Reverse transcription-polymerase chain reaction (RT-PCR) and protein immunoblot analyses were performed on serum from all 160 patients. No viremia was detected in any patient. Peripheral blood mononuclear cells from 159 of the patients were analyzed by PCR using PERV-specific primers. No PERV infection was detected in any of the patients from whom sufficient DNA was extracted to allow complete PCR analysis (97 percent of the patients). Persistent microchimerism (presence of donor cells in the recipient) was observed in 23 patients for up to 8.5 years.

1 Imutran Ltd. (a Novartis Pharma AG company), Post Office Box 399, Cambridge CB2 2YP, UK.
2 Genetic Therapy Inc. (a Novartis company), Gaithersburg, MD 20878, USA.
3 Centers for Disease Control and Prevention (National Center for Infectious Diseases, Division of AIDS, STD, and TB Laboratory Research, HIV and Retrovirology Branch), Atlanta, GA 30333, USA.
4 Q-One Biotech Ltd. and Department of Veterinary Pathology, University of Glasgow, Glasgow G20 OXA, UK.
5 Dmitry Shirokov (St. Petersburg, Russia); Achilles Demetriou (Los Angeles, CA, USA); Peter M. Vogt (Bochum, Germany); Annika Tibell and Carl Groth (Huddinge, Sweden); Robert Elliott (Auckland, New Zealand); Didier Samuel (Villejuif, France); Daniel Shouval (Jerusalem, Israel); Yaacov Baruch (Haifa, Israel); Ran Tur-Kaspar (Petach-Tikva, Israel); Michael E. Breimer (Göteborg, Sweden); A. Joseph Tector (Montreal, Canada); Claudy Mullon (Circe Biomedical, Lexington, KY, USA); Sabine Wehr and Kamal Abeywickrama (Novartis Pharma, Basel, Switzerland); Mi-Li Gu (GTI); Laurie O'Rourke (Imutran); Aprille Matthews, Vedapuri Shanmugam, and Althaf I. Hussain (CDC).
*   To whom correspondence should be addressed. E-mail: khazal.paradis{at}pharma.novartis.com

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Identification of Novel Porcine Endogenous Betaretrovirus Sequences in Miniature Swine.
T. Ericsson, B. Oldmixon, J. Blomberg, M. Rosa, C. Patience, and G. Andersson (2001)
J. Virol. 75, 2765-2770
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Multiple Groups of Novel Retroviral Genomes in Pigs and Related Species.
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J. Virol. 75, 2771-2775
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J. Virol. 75, 2825-2828
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Susceptibility of the Porcine Endogenous Retrovirus to Reverse Transcriptase and Protease Inhibitors.
S. H. Qari, S. Magre, J. G. García-Lerma, A. I. Hussain, Y. Takeuchi, C. Patience, R. A. Weiss, and W. Heneine (2001)
J. Virol. 75, 1048-1053
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Infectious Disease Issues in Xenotransplantation.
R. S. Boneva, T. M. Folks, and L. E. Chapman (2001)
Clin. Microbiol. Rev. 14, 1-14
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Physiologic and Immunologic Hurdles to Xenotransplantation.
B. SAMSTEIN and J. L. PLATT (2001)
J. Am. Soc. Nephrol. 12, 182-193
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Infection in the twenty-first century: predictions and postulates.
A. Geddes (2000)
J. Antimicrob. Chemother. 46, 873-877
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Antiretroviral Agents Inhibit Infection of Human Cells by Porcine Endogenous Retroviruses.
S. K. Powell, M. E. Gates, G. Langford, M.-L. Gu, C. Lockey, Z. Long, and E. Otto (2000)
Antimicrob. Agents Chemother. 44, 3432-3433
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Infection in xenotransplantation.
J. A Fishman (2000)
BMJ 321, 717-718
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Study of Full-Length Porcine Endogenous Retrovirus Genomes with Envelope Gene Polymorphism in a Specific-Pathogen-Free Large White Swine Herd.
S. Bösch, C. Arnauld, and A. Jestin (2000)
J. Virol. 74, 8575-8581
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Infection of Nonhuman Primate Cells by Pig Endogenous Retrovirus.
J. H. Blusch, C. Patience, Y. Takeuchi, C. Templin, C. Roos, K. Von Der Helm, G. Steinhoff, and U. Martin (2000)
J. Virol. 74, 7687-7690
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Starting clinical trials of xenotransplantation--reflections on the ethics of the early phase.
S. Welin (2000)
J. Med. Ethics 26, 231-236
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Establishment and Characterization of Molecular Clones of Porcine Endogenous Retroviruses Replicating on Human Cells.
F. Czauderna, N. Fischer, K. Boller, R. Kurth, and R. R. Tönjes (2000)
J. Virol. 74, 4028-4038
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Technological advances and the next 50 years of cardiology.
J. Flower, L. S. Dreifus, A. A. Bove, and W. S. Weintraub (2000)
J. Am. Coll. Cardiol. 35, 81B-90B
   PDF »
Xenotransplantation.
D. K C Cooper, C. G Groth, I. F C McKenzie, E. Goldman, A. Fano, and H. Y Vanderpool (2000)
BMJ 320, 868
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Technological advances and the next 50 years of cardiology.
J. Flower, L. S. Dreifus, A. A. Bove, and W. S. Weintraub (2000)
J. Am. Coll. Cardiol. 35, 1082-1091
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Transplantation of embryonic porcine mesencephalic tissue in patients with PD.
J. M. Schumacher, S. A. Ellias, E. P. Palmer, H. S. Kott, J. Dinsmore, P. K. Dempsey, A. J. Fischman, C. Thomas, R. G. Feldman, S. Kassissieh, et al. (2000)
Neurology 54, 1042-1050
   Abstract »    Full Text »    PDF »
Prevention of Acute Liver Failure in Rats with Reversibly Immortalized Human Hepatocytes.
N. Kobayashi, T. Fujiwara, K. A. Westerman, Y. Inoue, M. Sakaguchi, H. Noguchi, M. Miyazaki, J. Cai, N. Tanaka, I. J. Fox, et al. (2000)
Science 287, 1258-1262
   Abstract »    Full Text »
Xenotransplantation: postponed by a millennium?.
D. Candinas and D.H. Adams (2000)
QJM 93, 63-66
   Full Text »    PDF »
Xenotransplantation--2000.
M J Goddard, J E Foweraker, and J Wallwork (2000)
J. Clin. Pathol. 53, 44-48
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