Chapter 4 : Xenotransplantation

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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

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Equine infectious anemia virus
Mouse mammary tumor virus
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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
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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. 74:15491553.
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. 72:45034507.
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. 41:267279.
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. 44:4964.
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. 10:310.
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. 121:111.
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. 66:115123.
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 65:28162828.
10. Allan, J. S. 1994. Primates and new viruses. Science 265:13451346.
11. Allan, J. S. 1995. Xenograft transplantation and the infectious disease conundrum. ILAR J. 37:3748.
12. Allan, J. S. 1996. Xenotransplantation and possible emerging infectious diseases. Mol. Diagn. 1:118.
13. Allan, J. S. 1996. Xenotransplantation at a crossroads: prevention versus progress. Nat. Med. 2:1821.
14. Allan, J. S. 1997. Silk purse or sow's ear. Nat. Med. 3:275276.
15. Allan, J. S. 1998. The risk of using baboons as transplant donors. Exogenous and endogenous viruses. Ann. N. Y. Acad. Sci. 862:8799.
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 6:157168.
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. 142:28282834.
18. Bach, F. 1998. Xenotransplantation: problems and prospects. Annu. Rev. Med. 49:301310.
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. 121:139148.
20. Balayan, M. S. 1997. Epidemiology of hepatitis E virus infection. J. Viral Hepatitis 4:155165.
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. 32:5859.
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. 69:19031906.
23. Best, L.,, P. R. Le Tissier,, and J. P. Stoye. 1997. Endogenous retroviruses and the evolution of resistance to retroviral infection. Trends Microbiol. 5:313318.
24. Boeke, J. D.,, and J. P. Stoye,. 1997. Retrotransposons, endogenous retroviruses, and the evolution of retroelements, p. 343435. 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. 81:689694.
26. Bouillant, A. M.,, and A. S. Greig. 1975. Type C virus production by a continuous line of pig oviduct cells. J. Gen. Virol. 27:173180.
27. Brown, J.,, A. L. Matthews,, P. A. Sanstrom,, and L. E. Chapman. 1998. Xenotransplantation and the risk of retroviral zoonosis. Trends Microbiol. 6:411415.
28. Buhler, L.,, T. Friedman,, J. Iacomini,, and D. K. C. Cooper. 1999. Xenotransplantation— state of the art—update 1999. Front. Biosci. 4:D416D432.
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 17:195202.
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. 68:95105.
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. 66:68586867.
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 266:18651869.
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. 333:14981501.
37. Chapman, L. E. 1999. Xenogeneic infections and public health. Clin. Exp. Pharmacol. Physiol. 26:10051008.
38. Cooper, D. K. C.,, Y. Ye,, L. L. RolfJr.,, and N. Zuhdni,. 1991. The pig as a potential organ donor for man, p. 481500. 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. 141:3158.
40. Cozzi, E.,, and D. J. G. White. 1995. The generation of transgenic pigs as potential organ donors for humans. Nat. Med 1:964966.
41. Daar, A. S.,, and D. Phil. 1997. Ethics of xenotransplantation: animal issues, consent, and likely transformation of transplant ethics. World J. Surg. 21:975982.
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. 3:350353.
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 75:295305.
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. 11:991996.
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. 53:431133.
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. 7:525539.
49. Edington, N.,, R. G. Watt,, and W. Plowright. 1976. Cytomegalovirus excretion in gnoto-biotic pigs. J. Hyg. (Lond.) 77:283290.
50. Edington, N.,, R. G. Watt,, and W. Plowright. 1977. Experimental transplacental transmission of porcine cytomegalovirus. J. Hyg. (Lond.) 78:243251.
51. Edington, N.,, A. E. Wrathall,, and J. T. Done. 1988. Porcine cytomegalovirus (PCMV) in early gestation. Vet. Microbiol. 17:117128.
52. Edington, N., 1992. Cytomegalovirus, p. 250256. 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. 134:680681.
54. Ehlers, B.,, S. Ulrich,, and M. Goltz. 1999. Detection of two novel porcine herpesviruses with high similarity to gammaherpesviruses. J. Gen. Virol. 80:971978.
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. 39:4451.
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. 11:314.
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:S41S45.
59. Fishman, J. A. 1999. Infection in xenotransplantation: a clinical approach. Transplant. Proc. 31:22252227.
60. Florencio, P. S.,, and T. Caulfield. 1999. Xenotransplantation and public health: identifying the legal issues. Can. J. Public Health 90:282284.
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. 160:15191531.
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 84:13691373.
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. 57:17301737.
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 358:495499.
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 68:74337447.
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 397:436441.
67. Gibbs, C. J.Jr.,, D. C. Gajdusek,, and H. Amyx,. 1979. Strain variation in the viruses of Creutzfeldt-Jakob disease and kuru, p. 87110. 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 96:80228027.
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. 24:559562.
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. 89:12231235.
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 72:52625267.
72. Hammer, C., 1997. Evolution: its complexity and impact on xenotransplantation, p. 716735. 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. 10771110. 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. 6:10621066.
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. 4:403407.
76. Hines, R. K.,, and P. D. Lukert. 1995. Porcine circovirus: a serological survey of swine in the United States. Swine Health Prod. 3:7173.
77. Ho, M.,, and J. S. Drummer,. 1995. Infections in transplant recipients, p. 27092717. 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 1455:403418.
80. Kabrane-Lazizi, Y.,, J. B. Fine,, J. Elm,, G. E. Glass,, H. Higa,, A. Diwan,, C. J. GibbsJr.,, 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. 61:331335.
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 273:228231.
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. 122:924.
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. 35:303307.
84. Lanza, R. P.,, D. K. C. Cooper,, and W. L. Chick. 1997. Xenotransplantation. Sci. Am. 277:5459.
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 4:3945.
86. Larsson, E.,, and G. Andersson. 1998. Beneficial role of human endogenous retroviruses: facts and hypotheses. Scand. J. Immunol. 48:329338.
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 6:725755.
88. Le Tissier, P.,, J. P. Stoye,, Y. Takeuchi,, C. Patience,, and R. A. Weiss. 1997. Two sets of human-tropic pig retrovirus. Nature 389:681682.
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 66:616619.
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. 8:11221130.
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 247:848852.
92. Makrides, S. C. 1998. Therapeutic inhibition of the complement system. Pharmacol. Rev. 50:5987.
93. Mandel, T. E.,, and N. Koulmanda. 1994. Xenotransplantation of islets of Langerhans in diabetes mellitus. Transplant. Proc. 26:11101112.
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. 71:25622566.
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. 78:221227.
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. 79:21712179.
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 94:98609865.
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. 143:14051415.
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. 72:97149721.
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. 59:297302.
101. Michaels, M. G.,, and R. L. Simmons. 1994. Xenotransplantation: concerns aired over potential new infections. ASM News 61:442443.
102. Michaels, M. G., and R. L. Simmons. 1994. Xenotransplantation-associated zoonoses: strategies for prevention. Transplantation 57:17.
103. Michaels, M. G. 1997. Infectious concerns of cross-species transplantation: xenozoonoses. World J. Surg. 21:968974.
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. 73:35823586.
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 57:179188.
106. Mollnes, T. E.,, and A. E. Fiane. 1999. Xenotransplantation: how to overcome the complement obstacle? Mol. Immunol. 36:269276.
107. Morgan, F. 1997. Babe the magnificent organ donor? The perils and promises surrounding xenotransplantation. J. Contemp. Health Law Policy 14:127160.
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. 36:25352541.
109. Morse, S. S.,, and A. Schluederberg. 1990. Emerging viruses: the evolution of viruses and viral diseases. J. Infect. Dis. 162:17.
110. Murphy, F. A. 1994. New, emerging and reemerging infectious diseases. Adv. Virus Res. 4:152.
111. Myers, G.,, K. Maclnnes,, and B. Korber. 1992. The emergence of simian/human immunodeficiency viruses. AIDS Res. Hum. Retroviruses 8:373386.
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. 67:60256032.
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 92:24892493.
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. 74:11321139.
117. Onions, D. E., 1994. Viruses as the aetiological agents of leukaemia and lymphomas, p. 3471. 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. 11:430431.
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. 61:11191123.
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 285:12361241.
121. Pastoret, P. P.,, S. Escutenaire,, and B. Brochier. 1999. Zoonotic risks linked to xenotransplantation. Infect. Dis. Rev. 1:4779.
122. Patience, C.,, Y. Takeuchi,, and R. A. Weiss. 1997. Infection of human cells by an endogenous retrovirus of pigs. Nat. Med. 3:282286.
123. Patience, C.,, Y. Takeuchi,, and R. A. Weiss. 1998. Zoonosis in xenotransplantation. Curr. Opin. Immunol. 10:539542.
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. 4:269271.
125. Pool, R.. 1998. Saviors. Discover, May 1998, p. 5357.
126. Prescott, L. E., and P. Simmonds. 1998. Global distribution of transfusion-transmitted virus. N. Engl. J. Med. 339:776777.
127. Prusiner, S. B. 1982. Novel proteinaceous infectious particles cause scrapie. Science 216:136144.
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. 70:887897.
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. 339:13581363.
130. Riordan, S. M.,, and R. Williams. 1999. Extracorporeal support and hepatocyte transplantation in acute liver failure and cirrhosis. J. Gastroenterol. Hepatol. 14:757770.
131. Rose, R. M.,, K. B. Strans,, E. R. Schultz,, G. Schaefer,, G. W. RankinJr.,, 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. 71:41384144.
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. 13:181184.
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. 182:13451355.
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. 6:429435.
135. Sachs, D. H. 1994. The pig as a potential xenograft donor. Vet. Immunol. Immunopathol. 43:185191.
136. Satapathy, A. K.,, and B. Ravindram. 1999. Naturally occurring alpha-galactosyl antibodies in human sera display polyreactivity. Immunol. Lett. 69:347351.
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. 79:447456.
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. 4:1320.
140. Steele, D. J.,, and H. J. Auchincloss. 1995. Xenotransplantation. Annu. Rev. Med. 46:345360.
141. Stoye, J. P. 1997. Proviruses pose potential problems. Nature 386:126127.
142. Sun, Y. L.,, X. Ma,, D. Zhou,, I. Vacek,, and A. M. Sun. 1993. Porcine pancreatic islets: isolation, microencapsulation, and xenotransplantation. Artif. Organs 17:723733.
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. 145:818826.
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. 183:124128.
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 379:8588.
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. 71:6174r6178.
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. 72:99869991.
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 226:153167.
149. Tischer, I.,, H. Geldblom,, W. Vettermann,, and M. A. Koch. 1982. A very small porcine virus with circular single-stranded DNA. Nature 295:6466.
150. Tischer, I.,, W. Mields,, D. Wolff,, M. Vagt,, and W. Griem. 1986. Studies on epidemiology and pathogenicity of porcine circovirus. Arch. Virol. 91:271276.
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. 140:14271439.
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. 140:17991816.
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 58:6574.
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. 43:115120.
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 67:335343.
156. Tremblay, M. J.,, J.-E. Fortin,, and R. Cantin. 1998. The acquisition of host-encoded proteins by nascent HIV-1. Immunol. Today 19:346351.
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. 43:103122.
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. 80:31993205.
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 27:153157.
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. 80:24912499.
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. 13:50705074.
165. Weiss, R. A. 1998. Transgenic pigs and virus adaptation. Nature 391:327328.
166. Weiss, R. A. 1999 Xenografts and retroviruses. Science 285:12211222.
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. 44:267270.
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. 72:30823087.
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. 12:11841186.
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. 60:166171.
171. Wurzner, R. 1999. Evasion of pathogens by avoiding recognition or eradication by complement, in part via molecular mimicry. Mol. Immunol. 36:249260.
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 57:694703.
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 83:35693570.

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