[en] Although several major immunologic hurdles need to be overcome, the pig is currently considered the most likely source animal of cells, tissues and organs for transplantation into humans. Concerns have been raised with regard to the potential for the transfer of infectious agents with the transplanted organ to the human recipient. This risk is perceived to be increased as it is likely that the patient will be iatrogenically immunocompromised and the organ-source pig may be genetically engineered in such a way to render its organs particularly susceptible to infection with human viruses. Furthermore, the risk may not be restricted to the recipient, but may have consequences for the health of others in the community. The identification of porcine endogenous retroviruses and of hitherto unknown viruses have given rise to the most concern. We document here the agents we believe should be excluded from the organ-source pigs. We discuss the likelihood of achieving this aim and outline the potential means by which it may best be achieved.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Onions, David E.; Q-One Biotech
Cooper, David K.C.; Massachusetts General Hospital - MGH / Harvard Medical, School Boston > Transplantation Biology - Research Center
Alexander, Tom J.L.; University of Cambridge > Clinical Veterinary Medicine
Brown, Corrie C.; University of Georgia > College of Veterinary Medicine > Pathology
Claassen, Erwin A.W.; Institute for Animal Science and Health - DLO
Foweraker, Juliet E.; Papworth Hospital Cambridge > Public Health Laboratory Service > Microbiology Laboratory
Harris, Delbert L.Hank; State University Iowa. College of Veterinary Medicine > College of Agricuiture. Microbiology > Department of Veterinary Diagnostic and Production Animal Medicine
Mahy, Brian W.J.; National Center for infectious Diseases > Centers for Disease Control and Prevention
Minor, Phillip D.; National institute of Biological Standards and Control
Osterhaus, Albert D.M.E.; Erasmus Universiteit Rotterdam - EUR > Virology
Pastoret, Paul-Pierre ; Université de Liège - ULiège > Faculté de Médecine Vétérinaire > Immunologie Vaccinologie
Yamanouchi, Kazuya; Nippon Institute for Biological > Science
Language :
English
Title :
An approach to the control of disease transmission in pig-to-human xenotransplantation.
Institute of Medicine. Xenotransplantation: Science, Ethics, and Public Policy. Washington, DC, USA: National Academy Press, 1996.
VAN DER RIET F DE ST J, HUMAN PA, COOPER DKC, et al. Virological implications of the use of primates in xenotransplantation. Transplant Proc 1987; 19: 4068.
CHAPMAN LE, FOLKS TM, SALOMON DR, et al. Xenotransplantation and xenogeneic infections. N Engl J Med 1995; 333: 1498.
ALLAN JS. Xenotransplantation at a crossroads: prevention versus progress. Nature Med 1996; 2: 18.
BUTLER D. FDA warns on primate xenotransplants. Nature 1999; 398: 649.
COOPER DKC, YE Y, ROLF LL JR, ZUHDI N. The pig as a potential organ donor for man. In: COOPER DKC, KEMP E, REEMTSMA K, WHITE DJG, eds. Xenotransplantation, 1st edn. Heidelberg, Springer-Verlag, 1991, p. 481.
SACHS DH. The pig as a potential xenograft donor. Vet Immunol Immunopathol 1994; 43: 185.
COZZI E, WHITE DJG. The generation of transgenic pigspotential organ donors for humans. Nature Med 1995; 1: 964.
YE Y, NIEKRASZ M, KOSANKE S, et al. The pig as a potential organ donor for man: a study of potentially transferable disease from donor pig to recipient man. Transplantation 1994; 57: 694.
SMITH DM. Endogenous retroviruses in xenografting (Letter). N Engl J Med 1992; 328: 142.
FISHMAN JA. Miniature swine as organ donors for man: strategies for prevention of xenotransplant-associated infections. Xenotransplantation 1994; 1: 47.
STOYE JP, COFFIN JM. The dangers of Xenotransplantation. Nature Med 1995; 1: 1100.
PATIENCE C, TAKEUCHI Y, WEISS RA. Infection of human cells by an endogenous retrovirus of pigs. Nature Med 1997; 3: 282.
LE TISSIER P, STOYE J, TAKEUCHI Y, PATIENCE C, WEISS RA. Two sets of human-tropic pig retrovirus. Nature 1997; 389: 681.
ONIONS D, HART D, MAHONEY C, GALBRAITH D, SMITH K. Endogenous retroviruses and the safety of porcine xenotransplantation. Trends Microbiol 1998; 11: 430.
CHANG S-F, SGRO J-Y, PARRISH CR. Multiple amino acids in the capsid of canine parvovirus coordinately determine the canine host range and specific antigenic and haemagglutination properties. J Virol 1992; 66: 6858.
GAO F, BAILES E, ROBERTSON DL, et al. Origin of HIV-1 in the chimpanzee Pan troglodytes. Nature 1999; 397: 436.
GOOD AH, COOPER DKC, MALCOLM AJ, et al. Identification of carbohydrate structures which bind human antiporcine antibodies: implications for discordant xenografting in man. Transplant Proc 1992; 24: 559.
COOPER DKC, KOREN E, ORIOL R. Oligosaccharides and discordant xenotransplantation. Immunol Rev 1994; 141: 31.
GALILI U, MANDRELL RE, HAMADEH RM, SHOHET SB, GRIFFIS JM. The interaction between the human natural anti-α-galactosyl IgG (anti-Gal) and bacteria of the human flora. Infect Immun 1998; 57: 1730.
ROTHER RP, FODOR WL, SPRINGHORN JP, et al. A novel mechanism of retrovirus inactivation in human serum mediated by anti-α-galactosyl natural antibody. J Exp Med 1995; 182: 1345.
TAKEUCHI Y, PORTER CD, STRAHAN KM, et al. Sensitization of cells and retroviruses to human serum by (α1-3) galactosyltransferase. Nature 1996; 379: 85.
TAKEUCHI Y, LIONG SH, BIENIASZ PD, et al. Sensitization of rhabdo-, lenti-, and spumaviruses to human serum by galactosyl (α1-3) galactosylation. J Virol 1997; 71: 6174.
DOERIG RE, MARCIL A, CHOPRA A, RICHARDSON CD. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 1993; 75: 295.
WARD T, PIPKIN PA, CLARKSON NA, et al. Decay-accelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno-focal cloning method. EMBO J 1994; 13: 5070.
BERGELSON JM, MOHANTY JG, CROWELL RL, et al. Coxsackievirus B3 adapted to growth in RD cells binds to decay-accelerating factor (CD55). J Virol 1995; 69: 1903.
ALEXANDER TJL, THORNTON K, BOON G, LYSONS RJ, GUSH AF. Medicated early weaning to obtain pigs from pathogens endemic in the herd of origin. Vet Rec 1980; 106: 114.
HARRIS DL, ALEXANDER TJL. Methods of disease control. In: STRAW BE, D'ALLAIRE S, MENGELING WL, TAYLOR DJ, eds. Diseases of. Swine, 8th edn. Ames: Iowa State University Press, 1999, p. 1077.
RUBIN RH. Infections in the organ transplant recipient. In: RUBIN RH, YOUNG LS, eds. Clinical Approach to Infection in the Compromised Host, 3rd edn. New York: Plenum, 1994, p. 629.
FISHMAN JA, RUBIN RH. Opportunistic infections. In: COLVIN R, BAHN A, MCCLUSKEY RT, eds. Diagnostic Immunopathology. New York: Plenum, 1995, p. 283.
EASTLAND T. Infectious disease transmission through cell, tissue, and organ transplantation: reducing the risk through donor selection. Cell Transplantation 1995; 4: 455.
FOWERAKER JE, NEWSOM SWB. Bacterial, fungal and protozoal infection after transplantation of the heart and lungs. In: THIRU S, Waldmann H, eds. Pathology of Transplantation. Oxford: Oxford University Press, 2000.
FISHMAN JA. Xenosis and xenotransplantation: addressing the infectious risks posed by an emerging technology. Kidney Int 1997; 51(Suppl. 58): 41.
PATON NI, LEO YS, ZAKI SR, et al. Outbreak of Nipah-virus infection among abattoir workers in Singapore. Lancet 1999; 354: 1253.
CHUA KB, GOH KJ, WONG KT, et al. Fatal encephalitis due to Nipah virus among pig farmers in Malaysia. Lancet 1999; 354: 1257.
TRUYEN U, EVERMANN JF, VIELER E, PARRISH CR. Evolution of canine parvovirus involved loss and gain of feline host range. Virology 1996; 215: 186.
MENG X-J, PURCELL RH, HALBUR PG, et al. A novel virus in swine is closely related to the human hepatitis E virus. Proc Natl Acad Sci USA 1997; 94: 9860.
MENG X-J, HALBUR PG, SHAPIRO MS, et al. Genetic and experimental evidence for cross-species infection by swine hepatitis E virus. J Virol 1998; 72: 9714.
PHILBEY AW, KIRKLAND PD, ROSS AD, et al. An apparently new virus (family paramyxoviridae) infectious for pigs, humans, and fruit bats. Emerg Infect Dis 1998; 4: 269.
Centers for Disease Control and Prevention. Outbreak of Hendra-like virus - Malaysia and Singapore, 1998-99. MMWR Morb Mortal Wkly Rep 1999; 48: 265.
WOODS WA, PAPAS TS, HIRUMI H, CHIRIGOS MA. Antigenic and biochemical characterization of the C-type particle of the stable porcine kidney cell line PK15. J Virol 1973; 12: 1184.
TODARO GJ, BIENVENISTE RE, LIEBER MM, SHERR CJ. Characteristics of a Type C virus released from the porcine cell line PK (15). Virology 1974; 58: 65.
MOENNIG V, FRANK H, HUNSMANN G. et al. C-type particles produced by a permanent cell line from a leukemic pig. Virology 1974; 57: 179.
BOUILLANT AMP, GREIG AS, LIEBER MM, TODARO GJ. Type C virus production by a continuous line of pig oviduct cells. J Gen Virol 1975; 27: 173.
LIEBER MM, SHERR CJ, BIENEVENISTE RE, TODARO GJ. Biologic and immunologic properties of porcine type C viruses. Virology 1975; 66: 616.
SUZUKA I, SEKIGUCHI K, KODAMA M. Some characteristics of a porcine retrovirus from a cell line derived from swine malignant lymphomas. FEBS Lett 1985; 183: 124.
TAKEUCHI Y, PATIENCE C, MAGRE S, et al. Host range and interference studies of three classes of pig endogenous retrovirus. J Virol 1999; 72: 9986.
Q-One Biotech Ltd & Imutran Ltd. International patent application WO 97/40167 (Genbank accession number A66553), 1997.
AKIYOSHI DE, DENARO M, GREENSTEIN JL, et al. Identification of a full-length cDNA for an endogenous retrovirus of miniature swine. J Virol 1998; 72: 4503(Genbank accession numbers AF038600, AF038601, and AF038599).
WILSON CA, WONG S, MULLER J, et al. Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells. J Virol 1998; 72: 3082.
ONIONS DE. Viruses as the aetiological agents of leukaemia and lymphoma. In: BURNETT A, ARMITAGE J, NEWLAND A, KEATING A, eds. Cambridge Medical Reviews: Haematological Onocology. Cambridge: Cambridge University Press, 1994, p. 35.
MARTIN U, KIESSIG V, BLUSCH JH, et al. Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells. Lancet 1998; 352: 692.
KATZ AK, SKALKA AM. Generation of diversity in retroviruses. Annu Rev Genet 1990; 24: 409.
HENEINE W, TIBELL A, SWITZER WM, et al. No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts. Lancet 1998; 352: 695.
PATIENCE C, PATTON GS, TAKEUCHI Y, et al. No evidence of pig DNA or retroviral infection in patients with short-term extracorporeal connection to pig kidneys. Lancet 1998; 352: 699.
PARADIS K, LANGFORD G, LONG Z, et al. Search for cross-species transmission of porcine endogenous retrovirus in patients with living pig tissue. Science 1999; 285: 1236.
WILL RG, IRONSIDE JW, ZEIDLER M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996; 347: 921.
BRUCE ME, WILL RG, IRONSIDE JW, et al. Transmission to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 498.
HILL AF, DESBRUSLAIS M, JOINER S, et al. The same prion strain causes vCJD and BSE. Nature 1997; 389: 448.
GIBBS CJ JR, GAJDUSEK DC, AMYX H. Strain variation in the viruses of Creutzfeldt-Jakob disease and Kuru. In: PRUSINER SB, HADLOW WJ, eds. Slow Transmissible Diseases of the Nervous System, Vol. 2. New York, USA: Academic Press, 1979, p. 87.
DAWSON M, WHALES GAH, PARKER BNJ, SCOTT AC. Primary parenteral transmission of bovine spongiform encephalopathy to a pig. Vet Rec 1990; 127: 338.
DAWSON M, WELLS GAH, PARKER BNJ, SCOTT AC. Transmission studies of BSE in cattle, hamsters, pigs and domestic fowl. In: BRADLEY B, SAVEY M, MARCHANT B, eds. Sub-acute spongiform encephalopathies. Dordrecht, Germany: Kluwer Academic, 1991, p. 25.
Animal Health 1997. Report of the Chief Veterinary Officer. London: HMSO, 1997, p. 22.
HUNTER N, CAIRNS D. Scrapie-free Merino and Poll Dorset sheep from Australia and New Zealand have normal frequencies of scrapie-susceptible PrP genotypes. J Gen Virol 1998; 79: 2079.
RUBIN RH. The indirect effects of cytomegalovirus infection on the outcome of organ transplantation. (Editorial). Journal of the American Medical Association 1989; 261: 3607.
HO M, MILLER G, ATCHISON W, et al. Epstein-Barr virus infections and DNA hybridization studies in post-transplantation lymphoma and lymphoproliferative lesions: the role of primary infection. J Infect Dis 1985; 152: 876.
HANTO DW. Classification of Epstein-Barr virus-associated post-transplant lymphoproliferative diseases: implications for understanding their pathogenesis and developing rational treatment strategics. Annu Rev Med 1995; 46: 381.
HOY WE, ROBERTS NJ JR, BRYSON MF, et al. Transmission of strongyloidiasis by kidney transplant? Disseminated strongyloidiasis in both recipients of kidney allografts from a single cadaver donor. JAMA 1981; 246: 1937.
PERSING DH. Nucleic acid-based discovery techniques for potential xenozoonotic pathogens. In: COOPER DKC, KEMP E, PLATT JL, WHITE DJG, eds. Xenotransplantation, 2nd edn. Heidelberg: Springer-Verlag, 1997, p. 748.
