Correspondence

Endogenous Retroviruses in Xenografts

N Engl J Med 1993; 328:142-143January 14, 1993

Article

To the Editor:

Pressed by the increasing shortage of human organs, we are rapidly moving toward the use of xenografts from pigs or nonhuman primates. We must ask whether endogenous animal retroviruses pose any public health risk when transplanted into a human host.

Endogenous porcine retroviruses are not believed to undergo acute transformation; however, the expression of retroviruses has been associated with the development of leukemia and lymphoma in pigs1. Little is known about their structure, their similarities to other retroviruses, or the mechanism of their association with malignant diseases. Since these viral genomes are coded in the genomic DNA of pigs, all tissues may potentially express these viruses. Indeed, most cell lines derived from porcine tissues actively produce type C retroviruses2. Transplantation will put these retroviruses in intimate contact with human tissues.

Intimate contact alone will not result in the infection of human host tissues, since the porcine retroviruses that have been tested have a limited range of hosts. However, should porcine and human retroviruses coinfect a cell, they may recombine to form a chimeric virus3. Recombination is common in cells infected by retroviruses4. Analysis of sequence data from a number of mammalian retroviruses indicates that recombination has taken place. There is evidence that although porcine retroviruses were unable to cause a productive infection in murine cells, they were able to rescue the replication-defective Kirsten murine sarcoma virus from mouse, rat, and mink cell lines that were nonproducers. Thus, the range of hosts permitting viral entry is wider than that permitting productive infection. Although these events may be uncommon, thousands of transplantations may be performed yearly if xenografts are successful, and these grafts will be present in their immunosuppressed hosts for decades.

The recent transplantation of a baboon liver into a patient at the University of Pittsburgh presents a similar situation. Baboons carry an endogenous retrovirus (BaEV) that is closely homologous to the Moloney murine leukemia virus and the avian reticuloendotheliosis virus4. BaEV is also known to infect and replicate in human cells in vitro.

Thus, there is a potential for the coinfection of human or graft cells, resulting in the emergence of recombinant retroviruses with unknown pathogenic potential. These new viruses may pose a threat not only to patients but also to their contacts. We should therefore seek to learn more about these animal retroviruses.

Douglas M. Smith, M.D., Ph.D.
University of Oklahoma Health Sciences Center, Oklahoma City, OK 73126

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Citing Articles (16)

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   Li Zhang, Hong Bu, Youping Li, Jingqiu Cheng. (2003) Xenozoonoses in xenotransplantation*. Progress in Natural Science 13:1, 13-16
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   David K. C. Cooper, Bernd Gollackner, David H. Sachs. (2002) W ILL THE P IG S OLVE THE T RANSPLANTATION B ACKLOG ?. Annual Review of Medicine 53:1, 133-147
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   James Z. Appel, Leo Buhler, David K. C. Cooper. (2001) The Pig as a Source of Cardiac Xenografts. Journal of Cardiac Surgery 16:5, 345-356
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   Dominic C. Borie, Daniel Eyraud, Emmanuel Boleslawski, Antoinette Lemoine, Myl??ne Sebagh, Donald V. Cramer, Jacqueline Roussi, Fran??oise Imbert-Bismut, Guy Germain, Laurent Hannoun. (2001) FUNCTIONAL METABOLIC CHARACTERISTICS OF INTACT PIG LIVERS DURING PROLONGED EXTRACORPOREAL PERFUSION: POTENTIAL FOR A UNIQUE BIOLOGICAL LIVER-ASSIST DEVICE1. Transplantation 72:3, 393-405
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   G. M. Abouna. (2001) The Humanitarian aspects of organ transplantation*. Transplant International 14:2, 117-123
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   D.K.C. Cooper, A.M. Keogh, J. Brink, P.A. Corris, W. Klepetko, R.N. Pierson, M. Schmoeckel, R. Shirakura, L. Warner Stevenson. (2000) Report of the xenotransplantation advisory committee of the international society for heart and lung transplantation:. The Journal of Heart and Lung Transplantation 19:12, 1125-1165
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   D. Onions, D. K. C. Cooper, T. J. L. Alexander, C. Brown, E. Claassen, J. E. Foweraker, D. L. Harris, B. W. J. Mahy, P. D. Minor, A. D. M. E. Osterhaus, P.-P. Pastoret, K. Yamanouchi. (2000) An approach to the control of disease transmission in pig-to-human xenotransplantation. Xenotransplantation 7:2, 143-155
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    Toshio Miki, Vladimir Subbotin, April L. Goller, Alessia Tandin, Abdul S. Rao, John J. Fung, Luis A. Valdivia. (1999) Role of UW solution and sodium nitroprusside in reperfusion of liver xenografts from guinea-pig to rat. Xenotransplantation 6:2, 117-122
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