Chapter 4 : Xenotransplantation

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Xenotransplantation, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818050/9781555812010_Chap04-1.gif /docserver/preview/fulltext/10.1128/9781555818050/9781555812010_Chap04-2.gif


This chapter reviews the microbiological risks of xenotransplantation as they currently exist, with the caveat that the technical tools of molecular biology are rapidly adding to our knowledge in leaps and bounds. The ethical issue for xenotransplantation from the microbiological aspect is the risk of introducing an unknown infectious agent into a naive human population versus the individual benefit of a life-giving organ transplantation and improved quality of life. There is a large database of information on pigs, from basic anatomy and physiology to specifics of their biochemistry and genome. Production of pigs in barrier facilities operated under very high standards of animal husbandry can consistently yield qualified-pathogen-free animals. The gibbon ape leukemia virus (GALV) behaves as an exogenous retrovirus, but DNA evidence points to the endogenous retrovirus of as the origin. Certainly, the expanding interest in pigs as organ donors has placed the subject of endogenous retroviruses, in particular the porcine endogenous retrovirus (PERV), front and center in the microbiological risk analysis of xenotransplantation. PERV mRNA has been identified at variable levels in all tissues examined, indicating that viral expression is not restricted. Transmission electron microscopy of tissues was negative, although virus-like particles (VLP) were detected in serum. Although the VLP did not bind antibodies against recombinant gag or whole virus, product-enhanced reverse transcriptase analysis produced positive results.

Citation: O'Rourke L. 2000. Xenotransplantation, p 59-84. In Brown C, Bolin C (ed), Emerging Diseases of Animals. ASM Press, Washington, DC. doi: 10.1128/9781555818050.ch4
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

phylogenetic tree. An unrooted phylogenetic tree of retroviruses based on alignment of Pol amino acid sequences is shown. The tree was constructed from an alignment of 16 representative retrovirus sequences, corresponding to amino acids 178 to 740 of the predicted PERV-A Pol polyprotein. The values given at the branch forks are the bootstrap percentages for 2,000 samplings, with missing values all being 100%. Sequences were aligned using the CLUSTAL W program, and the PHYLIP package was used for protein distance calculation and tree construction. The solid line below the diagram represents 10% divergence. Diagram courtesy of D. E. Onions, Q-One Biotech, Glasgow, United Kingdom. HSRV, human respiratory syncytial virus; BaEV, baboon endogenous virus; SFV, simian foamy virus; EIAV, equine infectious anemia virus; FIV, feline immunodeficiency virus; RSV, Rous sarcoma virus; MPMV, Mason-Pfizer monkey virus; MMTV, mouse mammary tumor virus; BLV, bovine leukemia virus.

Citation: O'Rourke L. 2000. Xenotransplantation, p 59-84. In Brown C, Bolin C (ed), Emerging Diseases of Animals. ASM Press, Washington, DC. doi: 10.1128/9781555818050.ch4
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Abe, K.,, T. Inami,, K. Ishikawa,, S. Nakamura,, and S. Goto. 2000. TT virus infection in nonhuman primates and characterization of the viral genome: identification of simian TT virus isolates. 74: 1549 1553.
2. Advisory Group of the Ethics of Xenotransplantation. 1997. Animal Tissues into Humans. Her Majesty's Stationery Office, London, United Kingdom.
3. Akiyoshi, D. E.,, M. Denaro,, H. Zhu,, J. L. Greenstein,, P. Banerjee,, and J. A. Fishman. 1998. Identification of a full-length cDNA for an endogenous retrovirus of miniature swine. J. Virol. 72: 4503 4507.
4. Allan, G. M.,, F. McNeilly,, J. C. Foster,, and B. M. Adair. 1994. Infection of leucocyte cell cultures derived from different species with pig circovirus. Vet. Microbiol. 41: 267 279.
5. Allan, G. M.,, F. McNeilly,, J. P. Cassidy,, G. A. C. Reilly,, B. Adair,, W. A. Ellis,, and M. S. McNulty. 1995. Pathogenesis of porcine circovirus, experimental infections of colostrum deprived piglets and examination of pig fetal material. Vet. Microbiol. 44: 49 64.
6. Allan, G. M.,, F. McNeilly,, S. Kennedy,, B. Daft,, E. G. Clarke,, J. A. Ellis,, D. M. Haines,, B. M. Meehan,, and B. M. Adair. 1998. Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe. J. Vet. Diagn. Investig. 10: 3 10.
7. Allan, G. M.,, S. Kennedy,, F. McNeilly,, J. C. Foster,, J. A. Ellis,, S. J. Krakowka,, B. M. Meehan,, and B. M. Adair. 1999. Experimental reproduction of severe wasting disease by co-infection of pigs with porcine circovirus and porcine parvovirus. J. Comp. Pathol. 121: 1 11.
8. Allan, G. M.,, F. McNeilly,, B. M. Meehan,, S. Kennedy,, D. P. Mackie,, J. A. Ellis,, E. G. Clark,, E. Espuna,, N. Saubi,, P. Riera,, A. Botner,, and C. E. Charreyre. 1999. Isolation and characterization of circoviruses from pigs with wasting syndromes in Spain, Denmark and Northern Ireland. Vet. Microbiol. 66: 115 123.
9. Allan, J. S.,, M. Short,, M. E. Taylor,, S. Su,, V. M. Hirsch,, P. R. Johnson,, G. M. Shaw,, and B. H. Hahn. 1991. Species-specific diversity among simian immunodeficiency viruses from African green monkeys. J. Virol 65: 2816 2828.
10. Allan, J. S. 1994. Primates and new viruses. Science 265: 1345 1346.
11. Allan, J. S. 1995. Xenograft transplantation and the infectious disease conundrum. ILAR J. 37: 37 48.
12. Allan, J. S. 1996. Xenotransplantation and possible emerging infectious diseases. Mol. Diagn. 1: 1 18.
13. Allan, J. S. 1996. Xenotransplantation at a crossroads: prevention versus progress. Nat. Med. 2: 18 21.
14. Allan, J. S. 1997. Silk purse or sow's ear. Nat. Med. 3: 275 276.
15. Allan, J. S. 1998. The risk of using baboons as transplant donors. Exogenous and endogenous viruses. Ann. N. Y. Acad. Sci. 862: 87 99.
16. Alwayn, I. P. J.,, M. Basker,, L. Buhler,, and D. K. C. Cooper. 1999. The problem of anti-pig antibodies in pig-to-primate xenografting: current and novel methods of depletion and/or suppression of production of anti-pig antibodies. Xenotransplantation 6: 157 168.
17. Avila, J. L.,, M. Rojas,, and U. Galili. 1989. Immunogenic Gal alpha l-3Gal carbohydrate epitopes are present on pathogenic American trypanosoma and leishmania. J. Immunol. 142: 2828 2834.
18. Bach, F. 1998. Xenotransplantation: problems and prospects. Annu. Rev. Med. 49: 301 310.
19. Balasch, M.,, J. Segales,, C. Rosell,, M. Domingo,, A. Mankertz,, A. Urniza,, and J. Plana-Duran. 1999. Experimental inoculation of conventional pigs with tissue homogenates from pigs with post-weaning multisystemic wasting syndrome. J. Comp. Pathol. 121: 139 148.
20. Balayan, M. S. 1997. Epidemiology of hepatitis E virus infection. J. Viral Hepatitis 4: 155 165.
21. Balayan, M. S.,, R. K. Usmanov,, D. I. Zamyatina,, and F. R. Karas. 1990. Brief report: experimental hepatitis E infection in domestic pigs. J. Med. Virol. 32: 58 59.
22. Bergelson, J. M.,, J. G. Mohanty,, R. L. Crowell,, N. F. St. John,, D. M. Lublin,, and R. W. Finberg. 1995. Coxsackievirus B3 adapted to growth in RD cells binds to decay-accelerating factor (CD55). J. Virol. 69: 1903 1906.
23. Best, L.,, P. R. Le Tissier,, and J. P. Stoye. 1997. Endogenous retroviruses and the evolution of resistance to retroviral infection. Trends Microbiol. 5: 313 318.
24. Boeke, J. D.,, and J. P. Stoye,. 1997. Retrotransposons, endogenous retroviruses, and the evolution of retroelements, p. 343 435. In J. M. Coffin,, S. H. Hughes,, and H. E. Varmus (ed.), Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
25. Borlongan, C. V.,, D. W. Cahill,, T. Freeman,, and P. R. Sanberg. 1994. Recent advances in neural transplantation: relevance to neurodegenerative disorders. J. Fla. Med. Assoc. 81: 689 694.
26. Bouillant, A. M.,, and A. S. Greig. 1975. Type C virus production by a continuous line of pig oviduct cells. J. Gen. Virol. 27: 173 180.
27. Brown, J.,, A. L. Matthews,, P. A. Sanstrom,, and L. E. Chapman. 1998. Xenotransplantation and the risk of retroviral zoonosis. Trends Microbiol. 6: 411 415.
28. Buhler, L.,, T. Friedman,, J. Iacomini,, and D. K. C. Cooper. 1999. Xenotransplantation— state of the art—update 1999. Front. Biosci. 4: D416 D432.
29. Cavallo, R.,, G. Valente,, C. Jemma,, G. Gribaudo,, S. Landolfo,, and G. Cavallo. 1994. Presence of murine retroviral sequences in human cell line transplanted in immunosuppressed SCID mice. Microbiologica 17: 195 202.
30.. Centers for Disease Control and Prevention. 1997. Nonhuman primate spumavirus infections among persons with occupational exposure—United States, 1996. Morb. Mortal Wkly. Rep. 46: 129131.
31. Centers for Disease Control and Prevention. 1999. Outbreak of Hendra-like virus—Malaysia and Singapore, 1998-1999. Morb. Mortal. Wkly. Rep. 48: 265269. ( Erratum, 48:339.)
32. Centers for Disease Control and Prevention. 1999. Update: outbreak of Nipah virus— Malaysia and Singapore, 1999. Morb. Mortal. Wkly. Rep. 48: 335337.
33. Chandler, J. D.,, M. A. Riddell,, F. Ki,, R. J. Love,, and D. A. Anderson. 1999. Serological evidence for swine hepatitis E virus infection in Australian pig herds. Vet. Microbiol. 68: 95 105.
34. Chang, S. F.,, J. Y. Sgro,, and C. R. Parrish. 1992. Multiple amino acids in the capsid of canine parvovirus coordinately determine the canine host range and specific antigenic and haemagglutination properties. J. Virol. 66: 6858 6867.
35. Chang, Y.,, E. Cesarman,, M. S. Pessin,, F. Lee,, J. Culpepper,, D. M. Knowles,, and P. S. Moore. 1994. Identification of herpesvirus-like-DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266: 1865 1869.
36. Chapman, L. E.,, T. M. Folks,, D. R. Salomon,, A. P. Patterson,, T. E. Eggerman,, and P. D. Noguichi. 1995. Xenotransplantation and xenogeneic infections. N. Engl. J. Med. 333: 1498 1501.
37. Chapman, L. E. 1999. Xenogeneic infections and public health. Clin. Exp. Pharmacol. Physiol. 26: 1005 1008.
38. Cooper, D. K. C.,, Y. Ye,, L. L. Rolf Jr.,, and N. Zuhdni,. 1991. The pig as a potential organ donor for man, p. 481 500. In D. K. C. Cooper,, E. Kemp,, K. Reemtsma,, and D. J. G. White (ed.), Xenotransplantation, 1st ed. Springer, Heidelberg, Germany.
39. Cooper, D. K. C, E. Koren, and R. Oriol. 1994. Oligosaccharides and discordant xenotransplantation. Immunol. Rev. 141: 31 58.
40. Cozzi, E.,, and D. J. G. White. 1995. The generation of transgenic pigs as potential organ donors for humans. Nat. Med 1: 964 966.
41. Daar, A. S.,, and D. Phil. 1997. Ethics of xenotransplantation: animal issues, consent, and likely transformation of transplant ethics. World J. Surg. 21: 975 982.
42. Dawson, M.,, G. A. Wells,, B. N. Parker,, and A. C. Scott. 1990. Primary parenteral transmission of bovine spongiform encephalopathy to the pig. Vet. Rec. 127: 338.
43. Deacon, T.,, J. Schumacher,, J. Dinsmore,, C. Thomas,, P. Palmer,, S. Kott,, A. Edge,, D. Penney,, S. Kassissieh,, P. Dempsey,, and O. Isacson. 1997. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease. Nat Med. 3: 350 353.
44. Dorig, R. E.,, A. Marcil,, A. Chopra,, and C. D. Richardson. 1993. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 75: 295 305.
45. Dorland's Illustrated Medical Dictionary, 27th ed. 1988. W. B. Saunders, Philadelphia, Pa.
46. Dowling, D. J.,, and D. J. Mutimer. 1999. Artificial liver support in acute liver failure. Eur. J. Gastroenterol. Hepatol. 11: 991 996.
47. Dulac, G. C, and A. Ahmad. 1989. Porcine circovirus antigens in PK-15 cell line (ATCC CCL-33) and evidence of antibodies to circovirus in Canadian pigs. Can. J. Vet. Res. 53: 431 133.
48. Edge, A. S.,, M. E. Gosse,, and J. Dinsmore. 1998. Xenogeneic cell therapy: current progress and future developments in porcine cell transplantation. Cell Transplant. 7: 525 539.
49. Edington, N.,, R. G. Watt,, and W. Plowright. 1976. Cytomegalovirus excretion in gnoto-biotic pigs. J. Hyg. (Lond.) 77: 283 290.
50. Edington, N.,, R. G. Watt,, and W. Plowright. 1977. Experimental transplacental transmission of porcine cytomegalovirus. J. Hyg. (Lond.) 78: 243 251.
51. Edington, N.,, A. E. Wrathall,, and J. T. Done. 1988. Porcine cytomegalovirus (PCMV) in early gestation. Vet. Microbiol. 17: 117 128.
52. Edington, N., 1992. Cytomegalovirus, p. 250 256. In A. D. Leman,, B. E. Straw,, W. L. Mengeling,, S. D'Allaire,, and D. J. Taylor (ed.), Diseases of Swine, 7th ed. Iowa State University Press, Ames.
53. Edwards, S.,, and J. J. Sands. 1994. Evidence of circovirus infection in British pigs. Vet. Rec. 134: 680 681.
54. Ehlers, B.,, S. Ulrich,, and M. Goltz. 1999. Detection of two novel porcine herpesviruses with high similarity to gammaherpesviruses. J. Gen. Virol. 80: 971 978.
55. Ellis, J.,, L. Hassard,, E. Clark,, J. Harding,, G. Allan,, P. Willson,, J. Strokappe,, K. Martin, E McNeilly, B. Meehan, D. Todd, and D. Haines. 1998. Isolation of circovirus from lesions of pigs with postweaning multisystemic wasting syndrome. Can. Vet. J. 39: 44 51.
56. Ellis, J.,, S. Krakowka,, M. Lairmore,, D. Haines,, A. Bratanich,, E. Clark,, G. Allan,, C. Konoby,, L. Hassard,, B. Meehan,, K. Martin,, J. Harding,, S. Kennedy,, and F. McNeilly. 1999. Reproduction of lesions of postweaning multisystemic wasting syndrome in gnotobiotic piglets. J. Vet. Diagn. Investig. 11: 3 14.
57. Fishman, J.,, D. Sachs,, and R. Shaikh. 1998. Xenotransplantation: Scientific Frontiers and Public Policy. Ann. N. Y. Acad. Sci, vol. 862. New York Academy of Science, New York, N.Y.
58. Fishman, J. A. 1997. Xenosis and xenotransplantation: addressing the infectious risks posed by an emerging technology. Kidney Int. Suppl. 58: S41 S45.
59. Fishman, J. A. 1999. Infection in xenotransplantation: a clinical approach. Transplant. Proc. 31: 2225 2227.
60. Florencio, P. S.,, and T. Caulfield. 1999. Xenotransplantation and public health: identifying the legal issues. Can. J. Public Health 90: 282 284.
61. Galili, U.,, E. A. Rachmilewitz,, A. Peleg,, and I. Flechner. 1984. A unique natural human IgG antibody with anti-alpha-galactosyl specificity. J. Exp. Med. 160: 1519 1531.
62. Galili, U.,, M. R. Clark,, S. B. Shohet,, J. Buehler,, and B. A. Macher. 1987. Evolutionary relationship between the natural anti-Gal antibody and the Gal alpha 1→3Gal epitope in primates. Proc. Natl. Acad. Sci. USA 84: 1369 1373.
63. Galili, U.,, R. E. Mandrell,, R. M. Hamadeh,, S. B. Shohet,, and J. M. Griffis. 1998. The interaction between the human natural anti-α-galactosyl IgG (anti-Gal) and bacteria of the human flora. Infect. Immun. 57: 1730 1737.
64. Gao, F.,, L. Yue,, A. T. White,, R. G. Pappas,, J. Barchue,, A. P. Hanson,, B. M. Greene,, P. M. Sharp,, G. M. Shaw,, and B. H. Hahn. 1992. Human infection by genetically-diverse SIVsm-related HIV-2 in west Africa. Nature 358: 495 499.
65. Gao, F.,, L. Yue,, D. L. Robertson,, S. C. Hill,, H. Hui,, R. J. Biggar,, A. E. Neequaye,, T. M. Whelan,, D. D. Ho,, and G. M. Shaw. 1994. Genetic diversity of human immunodeficiency virus type 2: evidence for distinct sequence subtypes with differences in virus biology. J. Virol 68: 7433 7447.
66. Gao, E.,, E. Bailes,, D. L. Robertson,, Y. Chen,, C. M. Rodenburg,, S. F. Michael,, L. B. Cummins,, L. O. Arthur,, M. Peeters,, G. M. Shaw,, P. M. Sharp,, and B. H. Hahn. 1999. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature 397: 436 441.
67. Gibbs, C. J. Jr.,, D. C. Gajdusek,, and H. Amyx,. 1979. Strain variation in the viruses of Creutzfeldt-Jakob disease and kuru, p. 87 110. In S. B. Prusiner, and W. J. Hadlow (ed.), Slow Transmissible Diseases of the Nervous System, vol. 2. Pathogenesis, Immunology, Virology, and Molecular Biology of the Spongiform Encephalopathies. Academic Press, New York, N.Y.
68. Gibbs, M. J.,, and G. F. Weiller. 1999. Evidence that a plant virus switched hosts to infect a vertebrate and then recombined with a vertebrate-infecting virus. Proc. Natl Acad. Sci. USA 96: 8022 8027.
69. Good, A. H.,, D. K. C. Cooper,, A. J. Malcolm,, R. M. Ippolito,, E. Koren,, F. A. Neethling,, Y. Ye,, L. R. Zuhdi,, and L. R. Lamontagne. 1992. Identification of carbohydrate structures which bind human anti-porcine antibodies: implications for discordant xenografting in man. Transplant. Proc. 24: 559 562.
70. Groth, C. G.,, A. Tibell,, L. Wennberg,, and O. Korsgren. 1996. Experimental and clinical experience with xenoislet transplantation. Transplant. Proc. 28: 3515.
70a.. Hamadeh, R. M.,, G. A. Jarvis,, U. Galili,, R. E. Mandrell,, P. Zhou,, and J. M. Griffiss. 1992. Human natural anti-Gal IgG regulates alternative complement pathway activation on bacterial surfaces. J. Clin. Investig. 89: 1223 1235.
71. Hamel, A. L.,, L. L. Lin,, and G. P. Nayar. 1998. Nucleotide sequence of porcine circovirus associated with postweaning multisystemic wasting syndrome in pigs. J. Virol 72: 5262 5267.
72. Hammer, C., 1997. Evolution: its complexity and impact on xenotransplantation, p. 716 735. In D. K. C. Cooper,, E. Kemp,, J. L. Platt,, and D. J. G. White (ed.), Xenotransplantation, 2nd ed. Springer, Heidelberg, Germany.
73. Harris, D. L.,, and T. J. L. Alexander,. 1999. Methods of disease control, p. 1077 1110. In B. E. Straw,, S. D'Allaire,, W. L. Mengeling,, and D. J. Taylor (ed.), Diseases of Swine, 8th ed. Iowa State University Press, Ames.
74. Heneine, W.,, N. W. Lerche,, T. Woods,, T. Spira,, J. M. Liff,, W. Eley,, J. L. Yee,, J. E. Kaplan,, and R. F. Khabbaz. 1993. The search for human infection with simian type D retroviruses. J. Acquir. Immune Defic. Syndr. 6: 1062 1066.
75. Heneine, W.,, W. M. Switzer,, P. Sandstrom,, J. Brown,, S. Vedapuri,, C. A. Schable,, A. S. Khan,, N. W. Lerche,, M. Schweizer,, D. Neumann-Haefelin,, L. E. Chapman,, and T. M. Folks. 1998. Identification of a human population infected with simian foamy viruses. Nat. Med. 4: 403 407.
76. Hines, R. K.,, and P. D. Lukert. 1995. Porcine circovirus: a serological survey of swine in the United States. Swine Health Prod. 3: 71 73.
77. Ho, M.,, and J. S. Drummer,. 1995. Infections in transplant recipients, p. 2709 2717. In G. L. Mandell,, J. E. Bennett,, and R. Dolin (ed.) Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases, 4th ed., vol. 2. Churchill Livingstone, New York, N.Y.
78.Institute of Medicine. 1996. Xenotransplantation: Science, Ethics, and Public Policy. National Academy Press, Washington, D.C.
79. Joziasse, D. H.,, and R. Oriol. 1999. Xenotransplantation: the importance of the Galαl,3Gal epitope in hyperacute vascular rejection. Biochim. Biophys. Acta 1455: 403 418.
80. Kabrane-Lazizi, Y.,, J. B. Fine,, J. Elm,, G. E. Glass,, H. Higa,, A. Diwan,, C. J. Gibbs Jr.,, X. J. Meng,, S. U. Emerson,, and R. H. Purcell. 1999. Evidence for widespread infection of wild rats with hepatitis E virus in the United States. Am. J. Trop. Med. Hyg. 61: 331 335.
81. Karp, C. L.,, M. Wysocka,, L. M. Wahl,, J. M. Ahearn,, P. J. Cuomo,, B. Sherry,, G. Trinchieri,, and D. E. Griffin. 1996. Mechanism of suppression of cell-mediated immunity by measles virus. Science 273: 228 231.
82. Kennedy, S.,, D. Moffett,, F. McNeilly,, B. Meehan,, J. Ellis,, S. Krakowka,, and G. M. Allan. 2000. Reproduction of lesions of postweaning multisystemic wasting syndrome by infection of conventional pigs with porcine circovirus type 2 alone or in combination with porcine parvovirus. J. Comp. Pathol. 122: 9 24.
83. Kiupel, M.,, G. W. Stevenson,, S. K. Mittal,, E. G. Clark,, and D. M. Haines. 1998. Circovirus-like viral associated disease in weaned pigs in Indiana. Vet. Pathol. 35: 303 307.
84. Lanza, R. P.,, D. K. C. Cooper,, and W. L. Chick. 1997. Xenotransplantation. Sci. Am. 277: 54 59.
85. Lanza, R. P.,, and D. K. C. Cooper. 1998. Xenotransplantation of cells and tissues: application to a range of diseases, from diabetes to Alzheimer's. Mol. Med. Today 4: 39 45.
86. Larsson, E.,, and G. Andersson. 1998. Beneficial role of human endogenous retroviruses: facts and hypotheses. Scand. J. Immunol. 48: 329 338.
87. Leib-Mosch, C.,, M. Bachmann,, R. Brack-Werner,, T. Werner,, V. Erfle,, and R. Hehlmann. 1992. Expression and biological significance of human endogenous retroviral sequences. Leukemia 6: 725 755.
88. Le Tissier, P.,, J. P. Stoye,, Y. Takeuchi,, C. Patience,, and R. A. Weiss. 1997. Two sets of human-tropic pig retrovirus. Nature 389: 681 682.
89. Lieber, M. M.,, C. J. Sherr,, R. E. Benveniste,, and G. J. Todaro. 1975. Biologic and immunologic properties of porcine type C viruses. Virology 66: 616 619.
90. Lu, C. Y.,, T. A. Khair-el-Din,, I. A. Dawidson,, T. M. Butler,, K. M. Brasky,, M. A. Vazquez,, and S. C. Sicher. 1994. Xenotransplantation. FASEB J. 8: 1122 1130.
91. Lusso, P.,, F. Di Marzo Veronese,, B. Ensoli,, G. Franchini,, C. Jemma,, S. De Rocco,, V. S. Kalyanaraman,, and R. C. Gallo. 1990. Expanded HTV-1 cellular tropism by phenotypic mixing with murine endogenous retroviruses. Science 247: 848 852.
92. Makrides, S. C. 1998. Therapeutic inhibition of the complement system. Pharmacol. Rev. 50: 59 87.
93. Mandel, T. E.,, and N. Koulmanda. 1994. Xenotransplantation of islets of Langerhans in diabetes mellitus. Transplant. Proc. 26: 1110 1112.
94. Mankertz, A.,, F. Persson,, J. Mankertz,, G. Blaess,, and H. J. Buhk. 1997. Mapping and characterization of the origin of DNA replication of porcine circovirus. J. Virol. 71: 2562 2566.
95. Meehan, B. M.,, J. K. Creelan,, M. S. McNulty,, and D. Toss. 1997. Sequence of porcine circovirus DNA: affinities with plant circoviruses. J. Gen. Virol. 78: 221 227.
96. Meehan, B. M.,, F. McNeilly,, D. Todd,, S. Kennedy,, V. A. Jewhurst,, J. A. A. Ellis,, L. E. Hassard,, E. G. Clark,, D. M. Haines,, and G. M. Allan. 1998. Characterization of novel circovirus DNAs associated with wasting syndromes in pigs. J. Gen. Virol. 79: 2171 2179.
97. Meng, X. J.,, R. H. Purcell,, P. G. Halbur,, J. R. Lehman,, D. M. Webb,, T. S. Tsareva,, J. S. Haynes,, B. J. Thacker,, and S. U. Emerson. 1997. A novel virus in swine is closely related to the human hepatitis E virus. Proc. Natl. Acad. Sci. USA 94: 9860 9865.
98. Meng, X. J.,, P. G. Halbur,, J. S. Haynes,, T. S. Tsareva,, J. D. Bruna,, R. L. Royer,, R. H. Purcell,, and S. U. Emerson. 1998. Experimental infection of pigs with the newly identified swine hepatitis E virus (swine HEV), but not with human strains of HEV. Arch. Virol. 143: 1405 1415.
99. Meng, X. J.,, P. G. Halbur,, M. S. Shapiro,, S. Govindarajan,, J. D. Bruna,, I. K. Mushahwar,, R. H. Purcell,, and S. U. Emerson. 1998. Genetic and experimental evidence for cross-species infection by swine hepatitis E virus. J. Virol. 72: 9714 9721.
100. Meng, X. J.,, S. Dea,, R. E. Engle,, R. Friendship,, Y. S. Lyoo,, T. Sirinarumitr,, K. Urairong,, D. Wang,, D. Wong,, D. Yoo,, Y. Zhang,, R. H. Purcell,, and S. U. Emerson. 1999. Prevalence of antibodies to the hepatitis E virus in pigs from countries where hepatitis E is common or is rare in the human population. J. Med. Virol. 59: 297 302.
101. Michaels, M. G.,, and R. L. Simmons. 1994. Xenotransplantation: concerns aired over potential new infections. ASM News 61: 442 443.
102. Michaels, M. G., and R. L. Simmons. 1994. Xenotransplantation-associated zoonoses: strategies for prevention. Transplantation 57: 1 7.
103. Michaels, M. G. 1997. Infectious concerns of cross-species transplantation: xenozoonoses. World J. Surg. 21: 968 974.
104. Miyata,, H. H. Tsunoda,, A. Kazi,, A. Yamada,, M. A. Khan,, J. Murakami,, T. Kamahora,, K. Shiraki,, and S. Hino. 1999. Identification of a novel GC-rich 113-nucleotide region to complete the circular, single-stranded DNA genome of TT virus, the first human circovirus. J. Virol. 73: 3582 3586.
105. Moennig, V.,, H. Frank,, G. Hunsmann,, P. Ohms,, H. Schwarz,, and W. Schafer. 1974. C-type particles produced by a permanent cell line from a leukemic pig. Virology 57: 179 188.
106. Mollnes, T. E.,, and A. E. Fiane. 1999. Xenotransplantation: how to overcome the complement obstacle? Mol. Immunol. 36: 269 276.
107. Morgan, F. 1997. Babe the magnificent organ donor? The perils and promises surrounding xenotransplantation. J. Contemp. Health Law Policy 14: 127 160.
108. Morozov, I.,, T. Sirinarumitr,, S. D. Sorden,, P. G. Halbur,, M. K. Morgan,, K. J. Yoon,, and P. S. Paul. 1998. Detection of a novel strain of porcine circovirus in pigs with postweaning multisystemic wasting syndrome. J. Clin. Microbiol. 36: 2535 2541.
109. Morse, S. S.,, and A. Schluederberg. 1990. Emerging viruses: the evolution of viruses and viral diseases. J. Infect. Dis. 162: 1 7.
110. Murphy, F. A. 1994. New, emerging and reemerging infectious diseases. Adv. Virus Res. 4: 1 52.
111. Myers, G.,, K. Maclnnes,, and B. Korber. 1992. The emergence of simian/human immunodeficiency viruses. AIDS Res. Hum. Retroviruses 8: 373 386.
112. Naniche, D.,, G. Varior-Krishnan,, F. Cervoni,, T. F. Wild,, B. Rossi,, C. Rabourdin-Combe,, and D. Gerlier. 1993. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J. Virol. 67: 6025 6032.
113. Nishizawa, T.,, H. Okamoto,, K. Konishi,, H. Yoshizawa,, Y. Miyakawa,, and M. Mayumi. 1997. A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochem. Biophys. Res. Commun. 241: 92
114.Nuffield Council on Bioethics. 1996. Animal-to-human transplants: the Ethics of Xenotransplantation. Nuffield Council on Bioethics, London, United Kingdom.
115. Okada, N.,, M. K. Liszewski,, J. P. Atkinson,, and M. Caparon. 1995. Membrane cofactor protein (CD46) is a keratinocyte receptor for the M protein of the group A streptococcus. Proc. Natl Acad. Sci. USA 92: 2489 2493.
116. Okamoto, H.,, M. Fukuda,, A. Tawara,, T. Nishizawa,, Y. Itoh,, I. Hayasaka,, F. Tsuda,, T. Tanaka,, Y. Miyakawa,, and M. Mayumi. 2000. Species-specific TT viruses and cross-species infection in nonhuman primates. J. Virol. 74: 1132 1139.
117. Onions, D. E., 1994. Viruses as the aetiological agents of leukaemia and lymphomas, p. 34 71. In A. Burnett,, J. Armitage,, A. Newland,, and A. Keating (ed.) Cambridge Medical Reviews: Haematological Oncology. Cambridge University Press, Cambridge, United Kingdom.
117a. Onions, D.,, D. K. C. Cooper,, T. J. L. Alexander,, C. Brown,, E. Claassen,, J. Foweraker,, D. L. Harris,, B. Mahy,, A. D. M. E. Osterhaus,, P.-P. Pastoret,, K. Yamanouchi,, and P. Minor. An assessment of the risk of xenozoonotic disease in pig-to-human xenotransplantation. Xenotransplantation, in press.
118. Onions, D.,, D. Hart,, C. Mahoney,, D. Galbraith,, and K. Smith. 1998. Endogenous retroviruses and the safety of porcine xenotransplantation. Trends Microbiol. 11: 430 431.
119. Onuki, A.,, K. Abe,, K. Togashi,, K. Kawashima,, A. Taneichi,, and H. Tsunemitsu. 1999. Detection of porcine circovirus from lesions of a pig with wasting disease in Japan. J. Vet. Med. Sci. 61: 1119 1123.
120. Paridis, K.,, G. Langford,, Z. F. Long,, W. Heneine,, P. Sandstrom,, W. M. Switzer,, L. E. Chapman,, C. Lockey,, D. Onions,, the Xen 111 Working Group,, and E. Otto. 1999. Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. Science 285: 1236 1241.
121. Pastoret, P. P.,, S. Escutenaire,, and B. Brochier. 1999. Zoonotic risks linked to xenotransplantation. Infect. Dis. Rev. 1: 47 79.
122. Patience, C.,, Y. Takeuchi,, and R. A. Weiss. 1997. Infection of human cells by an endogenous retrovirus of pigs. Nat. Med. 3: 282 286.
123. Patience, C.,, Y. Takeuchi,, and R. A. Weiss. 1998. Zoonosis in xenotransplantation. Curr. Opin. Immunol. 10: 539 542.
124. Philbey, A. W.,, P. D. Kirkland,, A. D. Ross,, R. J. Davis,, A. B. Gleeson,, R. J. Love,, P. W. Daniels,, A. R. Gould,, and A. D. Hyatt. 1998. An apparently new virus (family Paramyxoviridae) infectious for pigs, humans, and fruit bats. Emerg. Infect. Dis. 4: 269 271.
125. Pool, R.. 1998. Saviors. Discover, May 1998, p. 53 57.
126. Prescott, L. E., and P. Simmonds. 1998. Global distribution of transfusion-transmitted virus. N. Engl. J. Med. 339: 776 777.
127. Prusiner, S. B. 1982. Novel proteinaceous infectious particles cause scrapie. Science 216: 136 144.
128. Purcell, D. F.,, C. M. Broscius,, E. F. Vanin,, C. E. Buckler,, A. W. Nienhuis,, and M. A. Martin. 1996. 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.
129. Regamey, N.,, M. Tamm,, M. Wernli,, A. Witschi,, G. Thiel,, G. Cathomas,, and P. Erb. 1998. Transmission of human herpesvirus 9 infection from renal-transplant donors to recipients. N. Engl. J. Med. 339: 1358 1363.
130. Riordan, S. M.,, and R. Williams. 1999. Extracorporeal support and hepatocyte transplantation in acute liver failure and cirrhosis. J. Gastroenterol. Hepatol. 14: 757 770.
131. Rose, R. M.,, K. B. Strans,, E. R. Schultz,, G. Schaefer,, G. W. Rankin Jr.,, M. E. Thouless,, C. C. Tsai,, and M. L. Bosch. 1997. Identification of two homologs of the Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in retroperitoneal fibromatosis of different macaque species. J. Virol. 71: 4138 4144.
132. Ross, R. S.,, S. Viazov,, V. Runde,, U. W. Schaefer,, and M. Roggendorf. 1999. Detection of TT virus DNA in specimens other than blood. J. Clin. Virol. 13: 181 184.
133. Rother, R. P.,, W. L. Fodor,, J. P. Springhorn,, C. W. Birks,, E. Setter,, M. S. Sandrin,, S. P. Squinto,, and S. A. Rollins. 1995a. A novel mechanism of retrovirus inactivation in human serum mediated by anti-α-galactosyl natural antibody. J. Exp. Med. 182: 1345 1355.
134. Rother, R. P.,, S. P. Squinto,, J. M. Mason,, and S. A. Rollins. 1995b. Protection of retroviral vector particles in human blood through complement inhibition. Hum. Gene Ther. 6: 429 435.
135. Sachs, D. H. 1994. The pig as a potential xenograft donor. Vet. Immunol. Immunopathol. 43: 185 191.
136. Satapathy, A. K.,, and B. Ravindram. 1999. Naturally occurring alpha-galactosyl antibodies in human sera display polyreactivity. Immunol. Lett. 69: 347 351.
137. Schlauder, G. G.,, G. J. Dawson,, J. C. Erker,, R. Y. Kwo,, M. F. Knigge,, D. L. Smalley,, J. E. Rosenblatt,, S. M. Desai,, and I. K. Mushahwar. 1998. The sequence and phylogenetic analysis of a novel hepatitis E virus isolated from a patient with acute hepatitis reported in the United States. J. Gen. Virol. 79: 447 456.
138. Simmonds, R.,, F. Davidson,, C. Lycett,, L. E. Prescott,, D. M. MacDonald,, J. Ellender,, P. L. Yap,, C. A. Ludlam,, G. H. Haydon,, J. Gillon,, and J. M. Jarvis. 1998. Detection of a novel DNA virus (TT virus) in blood donors and blood products. Lancet 352: 191.
139. Smith, A. W.,, D. E. Skilling,, N. Cherry,, J. H. Mead,, and D. O. Matson. 1998. Calicivirus emergence from ocean reservoirs: zoonotic and interspecies movements. Emerg. Infect. Dis. 4: 13 20.
140. Steele, D. J.,, and H. J. Auchincloss. 1995. Xenotransplantation. Annu. Rev. Med. 46: 345 360.
141. Stoye, J. P. 1997. Proviruses pose potential problems. Nature 386: 126 127.
142. Sun, Y. L.,, X. Ma,, D. Zhou,, I. Vacek,, and A. M. Sun. 1993. Porcine pancreatic islets: isolation, microencapsulation, and xenotransplantation. Artif. Organs 17: 723 733.
143. Sunil-Chandra, N. P.,, J. Amo,, J. Fazakerley,, and A. A. Nash. 1994. Lymphoproliferative disease in mice infected with murine gammaherpesvirus 68. Am. J. Pathol. 145: 818 826.
144. Suzuka, I.,, K. Sekiguchi,, and M. Kodama. 1985. Some characteristics of a porcine retrovirus from a cell line derived from swine malignant lymphomas. FEBS Lett. 183: 124 128.
145. Takeuchi, Y.,, C. D. Porter,, K. M. Strahan,, A. F. Preece,, K. Gustafsson,, F. L. Cosset,, R. A. Weiss,, and M. K. Collins. 1996. Sensitization of cells and retroviruses to human serum by (αl-3) galactosyltransferase. Nature 379: 85 88.
146. Takeuchi, Y.,, S. H. Liong,, P. D. Bieniasz,, U. Jager,, C. D. Porter,, T. Friedman,, M. O. McClure,, and R. A. Weiss. 1997. Sensitization of rhabdo-, lenti-, and spumaviruses to human serum by galactosyl (αl-3) galactosylation. J. Virol. 71: 6174r 6178.
147. Takeuchi, Y.,, C. Patience,, S. Magre,, R. A. Weiss,, P. T. Banerjee,, P. Le Tissier,, and J. P. Stoye. 1998. Host range and interference studies of three classes of pig endogenous retrovirus. J. Virol. 72: 9986 9991.
148. Tischer, I.,, R. Rasch,, and G. Tochtermann. 1974. Characterization of papovavirus- and picornavirus-like particles in permanent pig kidney cell lines. Zentbl. Bakteriol. Mikrobiol. Hyg. Ser. A 226: 153 167.
149. Tischer, I.,, H. Geldblom,, W. Vettermann,, and M. A. Koch. 1982. A very small porcine virus with circular single-stranded DNA. Nature 295: 64 66.
150. Tischer, I.,, W. Mields,, D. Wolff,, M. Vagt,, and W. Griem. 1986. Studies on epidemiology and pathogenicity of porcine circovirus. Arch. Virol. 91: 271 276.
151. Tischer, I.,, J. Bode,, H. Timm,, D. Peters,, R. Rasch,, S. Pociuli,, and E. Gerike. 1995. Presence of antibodies reacting with porcine circovirus in sera of humans, mice, and cattle. Arch. Virol. 140: 1427 1439.
152. Tischer, I.,, D. Peters,, and S. Pociuli. 1995. Occurrence and role of an early antigen and evidence for transforming ability of porcine circovirus. Arch. Virol. 140: 1799 1816.
153. Todaro, G. J.,, R. E. Benveniste,, M. M. Lieber,, and C. J. Sherr. 1974. Characteristics of a type C virus released from the porcine cell line PK15. Virology 58: 65 74.
154. Todaro, G. J.,, R. E. Benveniste,, C. J. Sherr,, M. M. Lieber,, and R. Callahan. 1975. Infectious primate type C virus group: evidence for an origin from an endogenous virus of the rodent, Mus caroli. Bibl. Haematol. 43: 115 120.
155. Todaro, G. J.,, M. M. Lieber,, R. E. Benveniste, and C J. Sherr. 1975. Infectious primate type C viruses: three isolates belonging to a new subgroup from the brains of normal gibbons. Virology 67: 335 343.
156. Tremblay, M. J.,, J.-E. Fortin,, and R. Cantin. 1998. The acquisition of host-encoded proteins by nascent HIV-1. Immunol. Today 19: 346 351.
157. Truyen, U.,, C. R. Parrish,, T. C. Harder,, and O.-R. Kaaden. 1995. There is nothing permanent except change: the emergence of new virus diseases. Vet. Microbiol. 43: 103 122.
158. Ulrich, S.,, M. Goltz,, and B. Ehlers. 1999. Characterization of the DNA polymerase loci of the novel porcine lymphotropic herpesviruses 1 and 2 in domestic and feral pigs. J. Gen. Virol. 80: 3199 3205.
159. U.S. Department of Health and Human Services, Food and Drug Administration. 1996. Draft Public Health Service guidelines on infectious disease issues in xenotransplantation. Fed. Register 61: 49929.
160. U.S. Department of Health and Human Services, Food and Drug Administration. 1999. Draft guidance for industry: precautionary measures to reduce the possible risk of transmission of zoonoses by blood and blood products from xenotransplantation product recipients and their contacts. Fed. Register 64: 73563.
161. U.S. Department of Health and Human Services, Food and Drug Administration. 1999. Guidance for industry: public health issues posed by the use of nonhuman primate xenografts. Fed. Register 64: 16743.
162. Vanderpool, H. Y. 1999. Commentary: a critique of Clark's frightening xenotransplantation scenario. J. Law Med. Ethics 27: 153 157.
163. Verschoor, E. J.,, S. Langenhuijzen,, and J. L. Heeney. 1999. TT viruses (TTV) of non-human primates and their relationship to the human TTV genotypes. J. Gen. Virol. 80: 2491 2499.
164. Ward, T.,, P. A. Pipkin,, N. A. Clarkson,, D. M. Stone,, P. D. Minor,, and J. W. Almond. 1994. Decay-accelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno-focal cloning method. EMBO J. 13: 5070 5074.
165. Weiss, R. A. 1998. Transgenic pigs and virus adaptation. Nature 391: 327 328.
166. Weiss, R. A. 1999 Xenografts and retroviruses. Science 285: 1221 1222.
166a. Wild, T. E.,, D. Naniche,, C. Rabourdin-Combe,, D. Gerlier,, E. Malvoisin,, V. Lecouturier,, and R. Buckland. 1995. Mode of entry of morbilliviruses. Vet. Microbiol. 44: 267 270.
167. Wilson, C. A.,, S. Wong,, J. Muller,, C. E. Davidson,, T. M. Rose,, and P. Burd. 1998. Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells. J. Virol. 72: 3082 3087.
168. Woods, W. A.,, T. S. Papas,, H. Hirumi,, and M. A. Chirigos. 1973. Antigenic and biochemical characterization of the C-type particle of the stable porcine kidney cell line PK15. J. Virol. 12: 1184 1186.
169.World Health Organization. 1997. Report of WHO consultation on xenotransplantation. World Health Organization, Geneva, Switzerland.
170. Wu, J. C.,, C. M. Chen,, T. Y. Chiang,, I. J. Sheen,, J. Y. Chen,, W. H. Tsai,, Y. H. Huang,, and S. D. Lee. 2000. Clinical and epidemiological implications of swine hepatitis E virus infection. J. Med. Virol. 60: 166 171.
171. Wurzner, R. 1999. Evasion of pathogens by avoiding recognition or eradication by complement, in part via molecular mimicry. Mol. Immunol. 36: 249 260.
172. Ye, Y.,, M. Niekrasz,, S. Kosanke,, R. Welsh,, H. E. Jordan,, J. C. Fox,, W. C. Edwards,, C. Maxwell,, and D. K. Cooper. 1994. The pig as a potential organ donor for man: a study of potentially transferable disease from donor pig to recipient man. Transplantation 57: 694 703.
173. Yokozaki, S.,, Y. Fukuda,, I. Nakano,, Y. Katano,, M. Okamura,, and M. Naruse. 1999. TT virus: a mother-to-child transmitted rather than bloodborne virus. Blood 83: 3569 3570.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error