Evaluierung der biologischen Sicherheit von Xenotransplantaten: Untersuchungen zur Übertragung von porzinen endogenen Retroviren in vitro und in vivo Markus Irgang1.1.111.2231.341.3.1378#3171.3.25601#2526603#1321.3.3605#29371.48602#45991.5102.2.12.1.110112.22.2.12.2.2122.2.3132.2.4142.2.52.2.6152.2.72.2.8162.32.3.12.3.2172.3.32.3.4182.3.52.42.4.12.4.2192.4.32.4.4202.4.52.4.621613#275223.3.12223607#283605#3663.224602#2853.3603#30725603#5093.426603#810273.5606#4943.628606#6843.729607#7143.83031608#6613.932609#3353.1033606#7293.1134603#39035606#6763.12606#8053.1336607#852374.4.137384.23940414.3424.44344455.454647LiteraturAbkürzungsverzeichnis603#856603#490 Danksagung ErklärungdeInhaltsverzeichnisHilfe Literatur Aaronson, S. A. and Stephenson, J. R. (1976): Endogenous type-C RNA viruses of mammalian cells, Biochim Biophys Acta, (vol. 458), No. 4, pp.323-54. Akiyoshi, D. E.; Denaro, M.; Zhu, H.; Greenstein, J. L.; Banerjee, P. and Fishman, J. A. (1998): Identification of a full-length cDNA for an endogenous retrovirus of miniature swine, J Virol, (vol. 72), No. 5, pp.4503-7. Alejandro, R.; Lehmann, R.; Ricordi, C.; Kenyon, N. S.; Angelico, M. C.; Burke, G.; Esquenazi, V.; Nery, J.; Betancourt, A. E.; Kong, S. S.; Miller, J. and Mintz, D. H. (1997): Long-term function (6 years) of islet allografts in type 1 diabetes, Diabetes, (vol. 46), No. 12, pp.1983-9. Allan, G. M. and Ellis, J. A. (2000): Porcine circoviruses: a review, J Vet Diagn Invest, (vol. 12), No. 1, pp.3-14. Allan, G. M.; Phenix, K. V.; Todd, D. and McNulty, M. S. (1994): Some biological and physico-chemical properties of porcine circovirus, Zentralbl Veterinarmed B, (vol. 41), No. 1, pp.17-26. Allan, J. S. (1998): The risk of using baboons as transplant donors. Exogenous and endogenous viruses, Ann N Y Acad Sci, (vol. 862), pp.87-99. Andersson, P.; Goldfarb, M. P. and Weinberg, R. A. (1979): A defined subgenomic fragment of in vitro synthesized Moloney sarcoma virus DNA can induce cell transformation upon transfection, Cell, (vol. 16), No. 1, pp.63-75. Argaw, T.; Colon-Moran, W. and Wilson, C. A. (2004): Limited infection without evidence of replication by porcine endogenous retrovirus in guinea pigs, J Gen Virol, (vol. 85), No. Pt 1, pp.15-9. Armstrong, J. A.; Porterfield, J. S. and De Madrid, A. T. (1971): C-type virus particles in pig kidney cell lines, J Gen Virol, (vol. 10), No. 2, pp.195-8. Baquerizo, A.; Mhoyan, A.; Kearns-Jonker, M.; Arnaout, W. S.; Shackleton, C.; Busuttil, R. W.; Demetriou, A. A. and Cramer, D. V. (1999): Characterization of human xenoreactive antibodies in liver failure patients exposed to pig hepatocytes after bioartificial liver treatment: an ex vivo model of pig to human xenotransplantation, Transplantation, (vol. 67), No. 1, pp.5-18. Bartosch, B.; Weiss, R. A. and Takeuchi, Y. (2002): PCR-based cloning and immunocytological titration of infectious porcine endogenous retrovirus subgroup A and B, J Gen Virol, (vol. 83), No. Pt 9, pp.2231-40. Bergelson, J. M.; Chan, M.; Solomon, K. R.; St John, N. F.; Lin, H. and Finberg, R. W. (1994): Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses, Proc Natl Acad Sci U S A, (vol. 91), No. 13, pp.6245-8. Berney, T.; Buhler, L.; Caulfield, A.; Oberholzer, J.; Toso, C.; Alejandro, R.; Cooper, D. K.; Ricordi, C. and Morel, P. (2001): Transplantation of islets of Langerhans: new developments, Swiss Med Wkly, (vol. 131), No. 47-48, pp.671-80. Besnier, C.; Takeuchi, Y. and Towers, G. (2002): Restriction of lentivirus in monkeys, Proc Natl Acad Sci U S A, (vol. 99), No. 18, pp.11920-5. Biggar, R. J.; Gigase, P. L.; Melbye, M.; Kestens, L.; Sarin, P. S.; Bodner, A. J.; Demedts, P.; Stevens, W. J.; Paluku, L.; Delacollette, C. and et al. (1985): ELISA HTLV retrovirus antibody reactivity associated with malaria and immune complexes in healthy Africans, Lancet, (vol. 2), No. 8454, pp.520-3. Billinis, C.; Paschaleri-Papadopoulou, E.; Psychas, V.; Vlemmas, J.; Leontides, S.; Koumbati, M.; Kyriakis, S. C. and Papadopoulos, O. (1999): Persistence of encephalomyocarditis virus (EMCV) infection in piglets, Vet Microbiol, (vol. 70), No. 3-4, pp.171-7. Blusch, J. H.; Patience, C.; Takeuchi, Y.; Templin, C.; Roos, C.; Von Der Helm, K.; Steinhoff, G. and Martin, U. (2000): Infection of nonhuman primate cells by pig endogenous retrovirus, J Virol, (vol. 74), No. 16, pp.7687-90. Bolli, G. B.; Di Marchi, R. D.; Park, G. D.; Pramming, S. and Koivisto, V. A. (1999): Insulin analogues and their potential in the management of diabetes mellitus, Diabetologia, (vol. 42), No. 10, pp.1151-67. Bosch, S.; Arnauld, C. and Jestin, A. (2000): Study of full-length porcine endogenous retrovirus genomes with envelope gene polymorphism in a specific-pathogen-free Large White swine herd, J Virol, (vol. 74), No. 18, pp.8575-81. Breese, S. S., Jr. (1970): Virus-like particles occurring in cultures of stable pig kidney cell lines. Brief report, Arch Gesamte Virusforsch, (vol. 30), No. 4, pp.401-4. Brenner, P.; Reichenspurner, H.; Schmoeckel, M.; Wimmer, C.; Rucker, A.; Eder, V.; Meiser, B.; Hinz, M.; Felbinger, T.; Hammer, C. and Reichart, B. (2000): Prevention of hyperacute xenograft rejection in orthotopic xenotransplantation of pig hearts into baboons using immunoadsorption of antibodies and complement factors, Transpl Int, (vol. 13 Suppl 1), pp.S508-17. Brewer, L. A.; Lwamba, H. C.; Murtaugh, M. P.; Palmenberg, A. C.; Brown, C. and Njenga, M. K. (2001): Porcine encephalomyocarditis virus persists in pig myocardium and infects human myocardial cells, J Virol, (vol. 75), No. 23, pp.11621-9. Buhler, L.; Friedman, T.; Iacomini, J. and Cooper, D. K. (1999): Xenotransplantation--state of the art--update 1999, Front Biosci, (vol. 4), pp.D416-32. Burns, D. P. and Temin, H. M. (1994): High rates of frameshift mutations within homo-oligomeric runs during a single cycle of retroviral replication, J Virol, (vol. 68), No. 7, pp.4196-203. Byrne, G. W.; McCurry, K. R.; Martin, M. J.; McClellan, S. M.; Platt, J. L. and Logan, J. S. (1997): Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage, Transplantation, (vol. 63), No. 1, pp.149-55. Byrne, G. W.; Schwarz, A.; Fesi, J. R.; Birch, P.; Nepomich, A.; Bakaj, I.; Velardo, M. A.; Jiang, C.; Manzi, A.; Dintzis, H.; Diamond, L. E. and Logan, J. S. (2002): Evaluation of different alpha-Galactosyl glycoconjugates for use in xenotransplantation, Bioconjug Chem, (vol. 13), No. 3, pp.571-81. CDC (1998): Fatal cercopithecine herpesvirus 1 (B virus) infection following a mucocutaneous exposure and interim recommendations for worker protection., Morb. Mortal. Wkly Rep., (vol. 47), pp.1073-1076. Chapman, L. E.; Folks, T. M.; Salomon, D. R.; Patterson, A. P.; Eggerman, T. E. and Noguchi, P. D. (1995): Xenotransplantation and xenogeneic infections., N Engl J Med, (vol. 333), pp.1498-501. Chapman, L. E. and Khabbaz, R. F. (1994): Etiology and epidemiology of the Four Corners hantavirus outbreak, Infect Agents Dis, (vol. 3), No. 5, pp.234-44. Chikobaeva, M. G.; Schatzl, H.; Rose, D.; Bush, U.; Iakovleva, L. A.; Deinhardt, F.; Helm, K. and Lapin, B. A. (1993): [A new variant of the simian T-lymphotropic retrovirus type I (STLV-IF) in the Sukhumi colony of hamadryas baboons], Vopr Virusol, (vol. 38), No. 6, pp.249-53. Chmielewicz, B.; Goltz, M.; Franz, T.; Bauer, C.; Brema, S.; Ellerbrok, H.; Beckmann, S.; Rziha, H. J.; Lahrmann, K. H.; Romero, C. and Ehlers, B. (2003): A novel porcine gammaherpesvirus, Virology, (vol. 308), No. 2, pp.317-29. Clark, D. A.; Fryer, J. F.; Tucker, A. W.; McArdle, P. D.; Hughes, A. E.; Emery, V. C. and Griffiths, P. D. (2003): Porcine cytomegalovirus in pigs being bred for xenograft organs: progress towards control, Xenotransplantation, (vol. 10), No. 2, pp.142-8. Clarke, M. F.; Trainor, C. D.; Mann, D. L.; Gallo, R. C. and Reitz, M. S. (1984): Methylation of human T-cell leukemia virus proviral DNA and viral RNA expression in short- and long-term cultures of infected cells, Virology, (vol. 135), No. 1, pp.97-104. Clemenceau, B.; Jegou, D.; Martignat, L. and Sai, P. (2001): Long-term follow-up failed to detect in vitro transmission of full-length porcine endogenous retroviruses from specific pathogen-free pig islets to human cells, Diabetologia, (vol. 44), No. 11, pp.2044-55. Clemenceau, B.; Jegou, D.; Martignat, L. and Sai, P. (2002): Microchimerism and transmission of porcine endogenous retrovirus from a pig cell line or specific pathogen-free pig islets to mouse tissues and human cells during xenografts in nude mice, Diabetologia, (vol. 45), No. 6, pp.914-23. Clemenceau, B.; Lalain, S.; Martignat, L. and Sai, P. (1999): Porcine endogenous retroviral mRNAs in pancreas and a panel of tissues from specific pathogen-free pigs, Diabetes Metab, (vol. 25), No. 6, pp.518-25. Coffin, J.M. (1996): Retroviridae and their replication., Fields, B.N. and et al, Eds, Virology, pp. 1767-1848, Raven Press,

New York

. Coffin, J.M.; Hughes, S.H. and Varmus, H.E. (1997): Retroviruses, Cold Spring Habour Laboratory Press,

Plainview (NY)

. Cooper, D. K.; Gollackner, B.; Knosalla, C. and Teranishi, K. (2002): Xenotransplantation--how far have we come?, Transpl Immunol, (vol. 9), No. 2-4, pp.251-6. Costa, C.; Zhao, L.; Burton, W. V.; Rosas, C.; Bondioli, K. R.; Williams, B. L.; Hoagland, T. A.; Dalmasso, A. P. and Fodor, W. L. (2002): Transgenic pigs designed to express human CD59 and H-transferase to avoid humoral xenograft rejection, Xenotransplantation, (vol. 9), No. 1, pp.45-57. Cowan, S.; Hatziioannou, T.; Cunningham, T.; Muesing, M. A.; Gottlinger, H. G. and Bieniasz, P. D. (2002): Cellular inhibitors with Fv1-like activity restrict human and simian immunodeficiency virus tropism, Proc Natl Acad Sci U S A, (vol. 99), No. 18, pp.11914-9. Cozzi, E.; Bhatti, F.; Schmoeckel, M.; Chavez, G.; Smith, K. G.; Zaidi, A.; Bradley, J. R.; Thiru, S.; Goddard, M.; Vial, C.; Ostlie, D.; Wallwork, J.; White, D. J. and Friend, P. J. (2000): Long-term survival of nonhuman primates receiving life-supporting transgenic porcine kidney xenografts, Transplantation, (vol. 70), No. 1, pp.15-21. Cozzi, E. and White, D. J. (1995): The generation of transgenic pigs as potential organ donors for humans, Nat Med, (vol. 1), No. 9, pp.964-6. Craighead, J. E.; Peralta, P. H.; Murnane, T. G. and Shelokov, A. (1963): Oral infection of swine with the encephalomyocarditis virus, J Infect Dis, (vol. 112), pp.205-12. Czauderna, F.; Fischer, N.; Boller, K.; Kurth, R. and Tonjes, R. R. (2000): Establishment and characterization of molecular clones of porcine endogenous retroviruses replicating on human cells, J Virol, (vol. 74), No. 9, pp.4028-38. Dalgard, D. W.; Hardy, R. J.; Pearson, S. L.; Pucak, G. J.; Quander, R. V.; Zack, P. M.; Peters, C. J. and Jahrling, P. B. (1992): Combined simian hemorrhagic fever and Ebola virus infection in cynomolgus monkeys, Lab Anim Sci, (vol. 42), No. 2, pp.152-7. Daniel, M. D.; Letvin, N. L.; Sehgal, P. K.; Hunsmann, G.; Schmidt, D. K.; King, N. W. and Desrosiers, R. C. (1987): Long-term persistent infection of macaque monkeys with the simian immunodeficiency virus, J Gen Virol, (vol. 68 ( Pt 12)), pp.3183-9. Deng, Y. M.; Tuch, B. E. and Rawlinson, W. D. (2000): Transmission of porcine endogenous retroviruses in severe combined immunodeficient mice xenotransplanted with fetal porcine pancreatic cells, Transplantation, (vol. 70), No. 7, pp.1010-6. Denner, J. (2001): Xenotransplantation, Transspezies-Übertragung von Retroviren und AIDS., Arndt, D, Obe, G, Kleeberg, U, Ed, Biotechnologische Verfahren und Möglichkeiten in der Medizin., pp. 164-183, Urban & Vogel Medien und Medizin Verlagsgesellschaft,

München

. Denner, J.; Norley, S. and Kurth, R. (1994): The Immunosuppressive peptide of HIV-1: functional domains and immune response in AIDS patients., AIDS, (vol. 8), pp.1063-72. Denner, J.; Phelps, R. C.; Löwer, R and Kurth, R. (1995): Antibody response of pregnant women, tumor and AIDS patients against the human endogenous retrovirus HERV-K., J Cancer Res Clin Oncol, (vol. 121), p.5. Denner, J.; Specke, V.; Schwendemann, J. and Tacke, S. J. (2001): Porcine endogenous retroviruses (PERVs): adaptation to human cells and attempts to infect small animals and non-human primates, Ann Transplant, (vol. 6), No. 3, pp.25-33. Denner, J.; Specke, V.; Tacke, S.J. and Boller, K. (2002): Porcine endogene Retroviren (PERVs): Erste Tiermodelle, hochsensitive Diagnostika und immunsuppressive Eigenschaften, Lison, AE, Ed, Transplantationsmedizin (vol. 14), pp. 231-245, Pabst Science Publishers,

Lengerich (Germany)

. Denner, J.; Specke, V.; Tacke, S.J. and Özel, M. (2002): Porcine Endogenous Retroviruses (PERVs): Diagnostic Assays, Adaptation to Human Cells and Infection Experiments with Small Animals and Non-human Primates, Lison, AE, Ed, Transplantationsmedizin (vol. 14), pp. 171-183, Pabst Science Publishers,

Lengerich (Germany)

. Denner, J.; Specke, V.; Thiesen, U.; Karlas, A. and Kurth, R. (2003): Genetic alterations of the long terminal repeat of an ecotropic porcine endogenous retrovirus during passage in human cells, Virology, (vol. 314), No. 1, pp.125-33. Dinsmore, J. H.; Manhart, C.; Raineri, R.; Jacoby, D. B. and Moore, A. (2000): No evidence for infection of human cells with porcine endogenous retrovirus (PERV) after exposure to porcine fetal neuronal cells, Transplantation, (vol. 70), No. 9, pp.1382-9. Dooldeniya, M. D. and Warrens, A. N. (2003): Xenotransplantation: where are we today?, J R Soc Med, (vol. 96), No. 3, pp.111-7. Dorig, R. E.; Marcil, A.; Chopra, A. and Richardson, C. D. (1993): The human CD46 molecule is a receptor for measles virus (Edmonston strain), Cell, (vol. 75), No. 2, pp.295-305. Dorling, A. (2003): Are anti-endothelial cell antibodies a pre-requisite for the acute vascular rejection of xenografts?, Xenotransplantation, (vol. 10), No. 1, pp.16-23. Dougherty, J. P. and Temin, H. M. (1988): Determination of the rate of base-pair substitution and insertion mutations in retrovirus replication, J Virol, (vol. 62), No. 8, pp.2817-22. Drosten, C.; Gunther, S.; Preiser, W.; van der Werf, S.; Brodt, H. R.; Becker, S.; Rabenau, H.; Panning, M.; Kolesnikova, L.; Fouchier, R. A.; Berger, A.; Burguiere, A. M.; Cinatl, J.; Eickmann, M.; Escriou, N.; Grywna, K.; Kramme, S.; Manuguerra, J. C.; Muller, S.; Rickerts, V.; Sturmer, M.; Vieth, S.; Klenk, H. D.; Osterhaus, A. D.; Schmitz, H. and Doerr, H. W. (2003): Identification of a novel coronavirus in patients with severe acute respiratory syndrome, N Engl J Med, (vol. 348), No. 20, pp.1967-76. Ehlers, B.; Ulrich, S. and Goltz, M. (1999): Detection of two novel porcine herpesviruses with high similarity to gammaherpesviruses, J Gen Virol, (vol. 80 ( Pt 4)), pp.971-8. Elliott, R. B.; Escobar, L.; Garkavenko, O.; Croxson, M. C.; Schroeder, B. A.; McGregor, M.; Ferguson, G.; Beckman, N. and Ferguson, S. (2000): No evidence of infection with porcine endogenous retrovirus in recipients of encapsulated porcine islet xenografts, Cell Transplant, (vol. 9), No. 6, pp.895-901. Ellis, J. A.; Bratanich, A.; Clark, E. G.; Allan, G.; Meehan, B.; Haines, D. M.; Harding, J.; West, K. H.; Krakowka, S.; Konoby, C.; Hassard, L.; Martin, K. and McNeilly, F. (2000): Coinfection by porcine circoviruses and porcine parvovirus in pigs with naturally acquired postweaning multisystemic wasting syndrome, J Vet Diagn Invest, (vol. 12), No. 1, pp.21-7. Ericsson, T. A.; Takeuchi, Y.; Templin, C.; Quinn, G.; Farhadian, S. F.; Wood, J. C.; Oldmixon, B. A.; Suling, K. M.; Ishii, J. K.; Kitagawa, Y.; Miyazawa, T.; Salomon, D. R.; Weiss, R. A. and Patience, C. (2003): Identification of receptors for pig endogenous retrovirus, Proc Natl Acad Sci U S A, (vol. 100), No. 11, pp.6759-64. Falcone, V.; Leupold, J.; Clotten, J.; Urbanyi, E.; Herchenroder, O.; Spatz, W.; Volk, B.; Bohm, N.; Toniolo, A.; Neumann-Haefelin, D. and Schweizer, M. (1999): Sites of simian foamy virus persistence in naturally infected African green monkeys: latent provirus is ubiquitous, whereas viral replication is restricted to the oral mucosa, Virology, (vol. 257), No. 1, pp.7-14. Fenaux, M.; Halbur, P. G.; Gill, M.; Toth, T. E. and Meng, X. J. (2000): Genetic characterization of type 2 porcine circovirus (PCV-2) from pigs with postweaning multisystemic wasting syndrome in different geographic regions of North America and development of a differential PCR-restriction fragment length polymorphism assay to detect and differentiate between infections with PCV-1 and PCV-2, J Clin Microbiol, (vol. 38), No. 7, pp.2494-503. Fiebig, U.; Stephan, O.; Kurth, R. and Denner, J. (2003): Neutralizing antibodies against conserved domains of p15E of porcine endogenous retroviruses: basis for a vaccine for xenotransplantation?, Virology, (vol. 307), No. 2, pp.406-13. Fishman, J. A. (1994): Miniature swine as organ donors for man: strategies for prevention of xenotransplant-associated infections, Xenotransplantation, (vol. 1), pp.47-49. Fryer, J. F.; Griffiths, P. D.; Fishman, J. A.; Emery, V. C. and Clark, D. A. (2001): Quantitation of porcine cytomegalovirus in pig tissues by PCR, J Clin Microbiol, (vol. 39), No. 3, pp.1155-6. Galbraith, D. N.; Kelly, H. T.; Dyke, A.; Reid, G.; Haworth, C.; Beekman, J.; Shepherd, A. and Smith, K. T. (2000): Design and validation of immunological tests for the detection of Porcine endogenous retrovirus in biological materials, J Virol Methods, (vol. 90), No. 2, pp.115-24. Galili, U. (2001): The alpha-gal epitope (Gal alpha 1-3Gal beta 1-4GlcNAc-R) in xenotransplantation, Biochimie, (vol. 83), No. 7, pp.557-63. Galili, U.; Anaraki, F.; Thall, A.; Hill-Black, C. and Radic, M. (1993): One percent of human circulating B lymphocytes are capable of producing the natural anti-Gal antibody, Blood, (vol. 82), No. 8, pp.2485-93. Gao, F.; Bailes, E.; Robertson, D. L.; Chen, Y.; Rodenburg, C. M.; Michael, S. F.; Cummins, L. B.; Arthur, L. O.; Peeters, M.; Shaw, G. M.; Sharp, P. M. and Hahn, B. H. (1999): Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes, Nature, (vol. 397), No. 6718, pp.436-41. Garkavenko, O.; Croxson, M. C.; Irgang, M.; Karlas, A.; Denner, J. and Elliott, R. B. (2004): Monitoring of potentially xenotic viruses in pig islet xenotransplantation, J Clin Microbiol, (vol. Im Druck). Gaumann, A.; Laudes, M.; Jacob, B.; Pommersheim, R.; Laue, C.; Vogt, W. and Schrezenmeir, J. (2000): Effect of media composition on long-term in vitro stability of barium alginate and polyacrylic acid multilayer microcapsules, Biomaterials, (vol. 21), No. 18, pp.1911-7. Gerlach, J. C. (1997): Long-term liver cell cultures in bioreactors and possible application for liver support, Cell Biol Toxicol, (vol. 13), No. 4-5, pp.349-55. Gerlach, J. C.; Brombacher, J.; Kloppel, K.; Schnoy, N. and Neuhaus, P. (1994): Comparison of four methods for mass hepatocyte isolation from pig and human livers, Transplantation, (vol. 57), pp.1318-22. Gessain, A. and de The, G. (1996): Geographic and molecular epidemiology of primate T lymphotropic retroviruses: HTLV-I, HTLV-II, STLV-I, STLV-PP, and PTLV-L, Adv Virus Res, (vol. 47), pp.377-426. Gill, R. Q. and Sterling, R. K. (2001): Acute liver failure, J Clin Gastroenterol, (vol. 33), No. 3, pp.191-8. Gillis, S. and Smith, K. A. (1977): Long term culture of tumour-specific cytotoxic T cells, Nature, (vol. 268), No. 5616, pp.154-6. Goff, S. P. (1996): Operating under a Gag order: a block against incoming virus by the Fv1 gene, Cell, (vol. 86), No. 5, pp.691-3. Goltz, M.; Ericsson, T.; Patience, C.; Huang, C. A.; Noack, S.; Sachs, D. H. and Ehlers, B. (2002): Sequence analysis of the genome of porcine lymphotropic herpesvirus 1 and gene expression during posttransplant lymphoproliferative disease of pigs, Virology, (vol. 294), No. 2, pp.383-93. Goltz, M.; Widen, F.; Banks, M.; Belak, S. and Ehlers, B. (2000): Characterization of the DNA polymerase loci of porcine cytomegaloviruses from diverse geographic origins, Virus Genes, (vol. 21), No. 3, pp.249-55. Gorbovitskaia, M.; Liu, Z.; Bourgeaux, N.; Li, N.; Lian, Z.; Chardon, P. and Rogel-Gaillard, C. (2003): Characterization of two porcine endogenous retrovirus integration loci and variability in pigs, Immunogenetics, (vol. 55), No. 4, pp.262-70. Gouvea, V. and Brantly, M. (1995): Is rotavirus a population of reassortants?, Trends Microbiol, (vol. 3), No. 4, pp.159-62. Graham, F. L.; Smiley, J.; Russell, W. C. and Nairn, R. (1977): Characteristics of a human cell line transformed by DNA from human adenovirus type 5, J Gen Virol, (vol. 36), No. 1, pp.59-74. Grant, R. F.; Malinak, C. J.; Wu, H.; Sabo, A. and Tsai, C. C. (1995): PCR amplification and DNA sequencing of SRV-2 from archived tumor tissues, Virus Res, (vol. 36), No. 2-3, pp.187-200. Groth, C. G.; Korsgren, O.; Tibell, A.; Tollemar, J.; Moller, E.; Bolinder, J.; Ostman, J.; Reinholt, F. P.; Hellerstrom, C. and Andersson, A. (1994): Transplantation of porcine fetal pancreas to diabetic patients, Lancet, (vol. 344), No. 8934, pp.1402-4. Groth, C. G.; Korsgren, O.; Wennberg, L.; Song, Z.; Wu, G.; Reinholt, F. and Tibell, A. (1998): Pig-to-human islet transplantation, Transplant Proc, (vol. 30), No. 7, pp.3809-10. Halbur, P. G.; Kasorndorkbua, C.; Gilbert, C.; Guenette, D.; Potters, M. B.; Purcell, R. H.; Emerson, S. U.; Toth, T. E. and Meng, X. J. (2001): Comparative pathogenesis of infection of pigs with hepatitis E viruses recovered from a pig and a human, J Clin Microbiol, (vol. 39), No. 3, pp.918-23. Hammer, C. and Thein, E. (2002): Physiological aspects of xenotransplantation, 2001, Xenotransplantation, (vol. 9), No. 5, pp.303-5. Hanger, J. J.; Bromham, L. D.; McKee, J. J.; O'Brien, T. M. and Robinson, W. F. (2000): The nucleotide sequence of koala (Phascolarctos cinereus) retrovirus: a novel type C endogenous virus related to Gibbon ape leukemia virus, J Virol, (vol. 74), No. 9, pp.4264-72. Heneine, W.; Switzer, W. M.; Sandstrom, P.; Brown, J.; Vedapuri, S.; Schable, C. A.; Khan, A. S.; Lerche, N. W.; Schweizer, M.; Neumann-Haefelin, D.; Chapman, L. E. and Folks, T. M. (1998): Identification of a human population infected with simian foamy viruses, Nat Med, (vol. 4), No. 4, pp.403-7. Heneine, W.; Switzer, W. M.; Soucie, J. M.; Evatt, B. L.; Shanmugam, V.; Rosales, G. V.; Matthews, A.; Sandstrom, P. and Folks, T. M. (2001): Evidence of porcine endogenous retroviruses in porcine factor VIII and evaluation of transmission to recipients with hemophilia, J Infect Dis, (vol. 183), No. 4, pp.648-52. Heneine, W.; Tibell, A.; Switzer, W. M.; Sandstrom, P.; Rosales, G. V.; Mathews, A.; Korsgren, O.; Chapman, L. E.; Folks, T. M. and Groth, C. G. (1998): No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts, Lancet, (vol. 352), No. 9129, pp.695-9. Herring, C.; Cunningham, D. A.; Whittam, A. J.; Fernandez-Suarez, X. M. and Langford, G. A. (2001): Monitoring xenotransplant recipients for infection by PERV, Clin Biochem, (vol. 34), No. 1, pp.23-7. Herring, C.; Quinn, G.; Bower, R.; Parsons, N.; Logan, N. A.; Brawley, A.; Elsome, K.; Whittam, A.; Fernandez-Suarez, X. M.; Cunningham, D.; Onions, D.; Langford, G. and Scobie, L. (2001): Mapping full-length porcine endogenous retroviruses in a large white pig, J Virol, (vol. 75), No. 24, pp.12252-65. Hofmann, W.; Schubert, D.; LaBonte, J.; Munson, L.; Gibson, S.; Scammell, J.; Ferrigno, P. and Sodroski, J. (1999): Species-specific, postentry barriers to primate immunodeficiency virus infection, J Virol, (vol. 73), No. 12, pp.10020-8. Holmes, G. P.; Chapman, L. E.; Stewart, J. A.; Straus, S. E.; Hilliard, J. K. and Davenport, D. S. (1995): Guidelines for the prevention and treatment of B-virus infections in exposed persons. The B virus Working Group, Clin Infect Dis, (vol. 20), No. 2, pp.421-39. Huang, L. H.; Silberman, J.; Rothschild, H. and Cohen, J. C. (1989): Replication of baboon endogenous virus in human cells. Kinetics of DNA synthesis and integration, J Biol Chem, (vol. 264), No. 15, pp.8811-4. Hubbard, G. B.; Soike, K. F.; Butler, T. M.; Carey, K. D.; Davis, H.; Butcher, W. I. and Gauntt, C. J. (1992): An encephalomyocarditis virus epizootic in a baboon colony, Lab Anim Sci, (vol. 42), No. 3, pp.233-9. Hughes, S. H.; Toyoshima, K.; Bishop, J. M. and Varmus, H. E. (1981): Organization of the endogenous proviruses of chickens: implications for origin and expression, Virology, (vol. 108), No. 1, pp.189-207. Hull, R. N.; Cherry, W. R. and Tritch, O. J. (1962): Growth characteristics of monkey kidney cell strains LLC-MK1, LLC-MK2, and LLC-MK2(NCTC-3196) and their utility in virus research, J Exp Med, (vol. 115), pp.903-18. Irgang, M.; Karlas, A.; Laue, C.; Specke, V.; Tacke, S.; Kurth, R.; Schrezenmeir, J. and Denner, J. (2004): Porcine endogenous retroviruses PERV-A and PERV-B infect neither mouse cells in vitro nor SCID mice in vivo, Intervirology, (vol. Im Druck). Irgang, M.; Sauer, I. M.; Karlas, A.; Zeilinger, K.; Gerlach, J. C.; Kurth, R.; Neuhaus, P. and Denner, J. (2003): Porcine endogenous retroviruses: no infection in patients treated with a bioreactor based on porcine liver cells, J Clin Virol, (vol. 28), No. 2, pp.141-54. Jainchill, J. L.; Aaronson, S. A. and Todaro, G. J. (1969): Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells, J Virol, (vol. 4), No. 5, pp.549-53. Jamieson, F. B.; Wang, E. E.; Bain, C.; Good, J.; Duckmanton, L. and Petric, M. (1998): Human torovirus: a new nosocomial gastrointestinal pathogen, J Infect Dis, (vol. 178), No. 5, pp.1263-9. Jin, H.; Inoshima, Y.; Wu, D.; Morooka, A. and Sentsui, H. (2000): Expression of porcine endogenous retrovirus in peripheral blood leukocytes from ten different breeds, Transpl Infect Dis, (vol. 2), No. 1, pp.11-4. Jones, P. A. and Takai, D. (2001): The role of DNA methylation in mammalian epigenetics, Science, (vol. 293), No. 5532, pp.1068-70. Joo, HS (1999): Encephalomyocarditis virus, Straw, BE, D'Allaire, S, Mengeling, WL, Taylor, DJ, Ed, Diseases of swine (vol. 8th Edition), pp. 139-144, Iowa State University Press,

Ames, Iowa

. Karlas, A.; Kurth, R. and Denner, J. (2004): Inhibition of porcine endogenous retroviruses by RNA interference: increasing the safety of xenotransplantation, Virology, (vol. 325), No. 1, pp.18-23. Kashmiri, S. V.; Mehdi, R.; Gupta, P. and Ferrer, J. F. (1985): Methylation and expression of bovine leukemia proviral DNA, Biochem Biophys Res Commun, (vol. 129), No. 1, pp.126-33. Kitamura, T.; Takano, M.; Hoshino, H.; Shimotohno, K.; Shimoyama, M.; Miwa, M.; Takaku, F. and Sugimura, T. (1985): Methylation pattern of human T-cell leukemia virus in vivo and in vitro: pX and LTR regions are hypomethylated in vivo, Int J Cancer, (vol. 35), No. 5, pp.629-35. Klymiuk, N.; Muller, M.; Brem, G. and Aigner, B. (2003): Recombination analysis of human-tropic porcine endogenous retroviruses, J Gen Virol, (vol. 84), No. Pt 10, pp.2729-34. Knowles, N. J.; Dickinson, N. D.; Wilsden, G.; Carra, E.; Brocchi, E. and De Simone, F. (1998): Molecular analysis of encephalomyocarditis viruses isolated from pigs and rodents in Italy, Virus Res, (vol. 57), No. 1, pp.53-62. Kobayashi, T.; Yokoyama, I.; Morozumi, K.; Nagasaka, T.; Hayashi, S.; Uchida, K.; Takagi, H. and Nakao, A. (2000): Comparative study of theefficacy of removal of anti-ABO and anti-gal antibodies by double filtration plasmapheresis, Xenotransplantation, (vol. 7), No. 2, pp.101-8. Koiwa, T.; Hamano-Usami, A.; Ishida, T.; Okayama, A.; Yamaguchi, K.; Kamihira, S. and Watanabe, T. (2002): 5'-long terminal repeat-selective CpG methylation of latent human T-cell leukemia virus type 1 provirus in vitro and in vivo, J Virol, (vol. 76), No. 18, pp.9389-97. Krach, U.; Fischer, N.; Czauderna, F. and Tonjes, R. R. (2001): Comparison of replication-competent molecular clones of porcine endogenous retrovirus class A and class B derived from pig and human cells, J Virol, (vol. 75), No. 12, pp.5465-72. Kroneman, A.; Cornelissen, L. A.; Horzinek, M. C.; de Groot, R. J. and Egberink, H. F. (1998): Identification and characterization of a porcine torovirus, J Virol, (vol. 72), No. 5, pp.3507-11. Ksiazek, T. G.; Erdman, D.; Goldsmith, C. S.; Zaki, S. R.; Peret, T.; Emery, S.; Tong, S.; Urbani, C.; Comer, J. A.; Lim, W.; Rollin, P. E.; Dowell, S. F.; Ling, A. E.; Humphrey, C. D.; Shieh, W. J.; Guarner, J.; Paddock, C. D.; Rota, P.; Fields, B.; DeRisi, J.; Yang, J. Y.; Cox, N.; Hughes, J. M.; LeDuc, J. W.; Bellini, W. J. and Anderson, L. J. (2003): A novel coronavirus associated with severe acute respiratory syndrome, N Engl J Med, (vol. 348), No. 20, pp.1953-66. Kuddus, R.; Patzer, J. F., 2nd; Lopez, R.; Mazariegos, G. V.; Meighen, B.; Kramer, D. J. and Rao, A. S. (2002): Clinical and laboratory evaluation of the safety of a bioartificial liver assist device for potential transmission of porcine endogenous retrovirus, Transplantation, (vol. 73), No. 3, pp.420-9. Kuiken, T.; Fouchier, R. A.; Schutten, M.; Rimmelzwaan, G. F.; van Amerongen, G.; van Riel, D.; Laman, J. D.; de Jong, T.; van Doornum, G.; Lim, W.; Ling, A. E.; Chan, P. K.; Tam, J. S.; Zambon, M. C.; Gopal, R.; Drosten, C.; van der Werf, S.; Escriou, N.; Manuguerra, J. C.; Stohr, K.; Peiris, J. S. and Osterhaus, A. D. (2003): Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome, Lancet, (vol. 362), No. 9380, pp.263-70. Kurth, R.; Teich, N. M.; Weiss, R. and Oliver, R. T. (1977): Natural human antibodies reactive with primate type-C viral antigens, Proc Natl Acad Sci U S A, (vol. 74), No. 3, pp.1237-41. Lai, L.; Kolber-Simonds, D.; Park, K. W.; Cheong, H. T.; Greenstein, J. L.; Im, G. S.; Samuel, M.; Bonk, A.; Rieke, A.; Day, B. N.; Murphy, C. N.; Carter, D. B.; Hawley, R. J. and Prather, R. S. (2002): Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning, Science, (vol. 295), No. 5557, pp.1089-92. Langford, G. A.; Cozzi, E.; Yannoutsos, N.; Lancaster, R.; Elsome, K.; Chen, P. and White, D. J. (1996): Production of pigs transgenic for human regulators of complement activation using YAC technology, Transplant Proc, (vol. 28), No. 2, pp.862-3. Langford, G. A.; Galbraith, D.; Whittam, A. J.; McEwan, P.; Fernandez-Suarez, X. M.; Black, J.; Shepherd, A. and Onions, D. (2001): In vivo analysis of porcine endogenous retrovirus expression in transgenic pigs, Transplantation, (vol. 72), No. 12, pp.1996-2000. Larsson, E.; Kato, N. and Cohen, M. (1989): Human endogenous proviruses, Curr Top Microbiol Immunol, (vol. 148), pp.115-32. Lavitrano, M.; Bacci, M. L.; Forni, M.; Lazzereschi, D.; Di Stefano, C.; Fioretti, D.; Giancotti, P.; Marfe, G.; Pucci, L.; Renzi, L.; Wang, H.; Stoppacciaro, A.; Stassi, G.; Sargiacomo, M.; Sinibaldi, P.; Turchi, V.; Giovannoni, R.; Della Casa, G.; Seren, E. and Rossi, G. (2002): Efficient production by sperm-mediated gene transfer of human decay accelerating factor (hDAF) transgenic pigs for xenotransplantation, Proc Natl Acad Sci U S A, (vol. 99), No. 22, pp.14230-5. Le Tissier, P.; Stoye, J. P.; Takeuchi, Y.; Patience, C. and Weiss, R. A. (1997): Two sets of human-tropic pig retrovirus, Nature, (vol. 389), No. 6652, pp.681-2. Lee, J. H.; Webb, G. C.; Allen, R. D. and Moran, C. (2002): Characterizing and mapping porcine endogenous retroviruses in Westran pigs, J Virol, (vol. 76), No. 11, pp.5548-56. Lerche, N. W.; Marx, P. A.; Osborn, K. G.; Maul, D. H.; Lowenstine, L. J.; Bleviss, M. L.; Moody, P.; Henrickson, R. V. and Gardner, M. B. (1987): Natural history of endemic type D retrovirus infection and acquired immune deficiency syndrome in group-housed rhesus monkeys, J Natl Cancer Inst, (vol. 79), No. 4, pp.847-54. Levy, M. F.; Crippin, J.; Sutton, S.; Netto, G.; McCormack, J.; Curiel, T.; Goldstein, R. M.; Newman, J. T.; Gonwa, T. A.; Banchereau, J.; Diamond, L. E.; Byrne, G.; Logan, J. and Klintmalm, G. B. (2000): Liver allotransplantation after extracorporeal hepatic support with transgenic (hCD55/hCD59) porcine livers: clinical results and lack of pig-to-human transmission of the porcine endogenous retrovirus, Transplantation, (vol. 69), No. 2, pp.272-80. Lieber, M. M.; Benveniste, R. E.; Livingston, D. M. and Todaro, G. J. (1973): Mammalian cells in culture frequently release type C viruses, Science, (vol. 182), No. 107, pp.56-9. Lilly, F. (1970): Fv-2: identification and location of a second gene governing the spleen focus response to Friend leukemia virus in mice, J Natl Cancer Inst, (vol. 45), No. 1, pp.163-9. Lindeborg, E.; Kumagai-Braesch, M.; Tibell, A. and Moller, E. (2001): Continued production of xenoimmune antibodies 6-8 years after clinical transplantation of fetal pig islet-like cell-clusters, Xenotransplantation, (vol. 8), No. 4, pp.273-83. Logan, J. S. (2000): Prospects for xenotransplantation, Curr Opin Immunol, (vol. 12), No. 5, pp.563-8. Loss, M.; Arends, H.; Winkler, M.; Przemeck, M.; Steinhoff, G.; Rensing, S.; Kaup, F. J.; Hedrich, H. J.; Winkler, M. E. and Martin, U. (2001): Analysis of potential porcine endogenous retrovirus (PERV) transmission in a whole-organ xenotransplantation model without interfering microchimerism, Transpl Int, (vol. 14), No. 1, pp.31-7. Lower, R.; Boller, K.; Hasenmaier, B.; Korbmacher, C.; Muller-Lantzsch, N.; Lower, J. and Kurth, R. (1993): Identification of human endogenous retroviruses with complex mRNA expression and particle formation, Proc Natl Acad Sci U S A, (vol. 90), No. 10, pp.4480-4. Lucchiari, N.; Azimzadeh, A.; Wolf, P.; Regnault, V. and Cinqualbre, J. (1997): In vivo and in vitro optimization of depletion of IgM and IgG xenoantibodies by immunoadsorption using cell membrane proteins, Artif Organs, (vol. 21), No. 4, pp.278-86. Luciw, P.A. and Leung, N.J. (1992): Mechanisms of retrovirus replication., Levy, JA, Ed, The retroviridae, pp. 159-298, Plenum Press,

New York

. Malchesky, P. S. (2004): Artificial organs 2003: a year in review, Artif Organs, (vol. 28), No. 4, pp.410-24. Mankertz, A.; Domingo, M.; Folch, J. M.; LeCann, P.; Jestin, A.; Segales, J.; Chmielewicz, B.; Plana-Duran, J. and Soike, D. (2000): Characterisation of PCV-2 isolates from Spain, Germany and France, Virus Res, (vol. 66), No. 1, pp.65-77. Mankertz, A.; Persson, F.; Mankertz, J.; Blaess, G. and Buhk, H. J. (1997): Mapping and characterization of the origin of DNA replication of porcine circovirus, J Virol, (vol. 71), No. 3, pp.2562-6. Manns, A.; Hisada, M. and La Grenade, L. (1999): Human T-lymphotropic virus type I infection, Lancet, (vol. 353), No. 9168, pp.1951-8. Mantovani, R. (1999): The molecular biology of the CCAAT-binding factor NF-Y, Gene, (vol. 239), No. 1, pp.15-27. Martin, U.; Kiessig, V.; Blusch, J. H.; Haverich, A.; von der Helm, K.; Herden, T. and Steinhoff, G. (1998): Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells, Lancet, (vol. 352), No. 9129, pp.692-4. Martin, U.; Steinhoff, G.; Kiessig, V.; Chikobava, M.; Anssar, M.; Morschheuser, T.; Lapin, B. and Haverich, A. (1998): Porcine endogenous retrovirus (PERV) was not transmitted from transplanted porcine endothelial cells to baboons in vivo, Transpl Int, (vol. 11), No. 4, pp.247-51. Martin, U.; Tacke, S. J.; Simon, A. R.; Schroder, C.; Wiebe, K.; Lapin, B.; Haverich, A.; Denner, J. and Steinhoff, G. (2002): Absence of PERV specific humoral immune response in baboons after transplantation of porcine cells or organs, Transpl Int, (vol. 15), No. 7, pp.361-8. Matthews, P. J. (2001): Zoonotic agents in swine-to-human xenotransplants, Platt, J. L., Ed, Xenotransplantation, pp. 217-238, American Society for Microbiology,

Washington, D.C.

. Mazariegos, G. V.; Kramer, D. J.; Lopez, R. C.; Shakil, A. O.; Rosenbloom, A. J.; DeVera, M.; Giraldo, M.; Grogan, T. A.; Zhu, Y.; Fulmer, M. L.; Amiot, B. P. and Patzer, J. F. (2001): Safety observations in phase I clinical evaluation of the Excorp Medical Bioartificial Liver Support System after the first four patients, Asaio J, (vol. 47), No. 5, pp.471-5. McIntyre, M. C.; Kannan, B.; Solano-Aguilar, G. I.; Wilson, C. A. and Bloom, E. T. (2003): Detection of porcine endogenous retrovirus in cultures of freshly isolated porcine bone marrow cells, Xenotransplantation, (vol. 10), No. 4, pp.337-42. Meng, X. J.; Halbur, P. G.; Shapiro, M. S.; Govindarajan, S.; Bruna, J. D.; Mushahwar, I. K.; Purcell, R. H. and Emerson, S. U. (1998): Genetic and experimental evidence for cross-species infection by swine hepatitis E virus, J Virol, (vol. 72), No. 12, pp.9714-21. Meng, X. J.; Purcell, R. H.; Halbur, P. G.; Lehman, J. R.; Webb, D. M.; Tsareva, T. S.; Haynes, J. S.; Thacker, B. J. and Emerson, S. U. (1997): A novel virus in swine is closely related to the human hepatitis E virus, Proc Natl Acad Sci U S A, (vol. 94), No. 18, pp.9860-5. Meyer, C.; Hering, B. J.; Grossmann, R.; Brandhorst, H.; Brandhorst, D.; Gerich, J.; Federlin, K. and Bretzel, R. G. (1998): Improved glucose counterregulation and autonomic symptoms after intraportal islet transplants alone in patients with long-standing type I diabetes mellitus, Transplantation, (vol. 66), No. 2, pp.233-40. Michaels, M. G. (2001): Xenotransplantation as a vector for infection, Platt, J. L., Ed, Xenotransplantation, pp. 193-206, American Society for Microbiology,

Washington, D.C.

. Miller, A. D.; Bonham, L.; Alfano, J.; Kiem, H. P.; Reynolds, T. and Wolgamot, G. (1996): A novel murine retrovirus identified during testing for helper virus in human gene transfer trials, J Virol, (vol. 70), No. 3, pp.1804-9. Modrow, S.; Falke, D. and Truyen, U. (2003): Retroviren, Molekulare Virologie (vol. 2. Auflage), pp. 390-448, Spektrum Akademischer Verlag GmbH,

Heidelberg, Berlin

. Mollnes, T. E. and Fiane, A. E. (2003): Perspectives on complement in xenotransplantation, Mol Immunol, (vol. 40), No. 2-4, pp.135-43. Mone, J.; Whitehead, E.; Leland, M.; Hubbard, G. and Allan, J. S. (1992): Simian T-cell leukemia virus type I infection in captive baboons, AIDS Res Hum Retroviruses, (vol. 8), No. 9, pp.1653-61. Morsiani, E.; Pazzi, P.; Puviani, A. C.; Brogli, M.; Valieri, L.; Gorini, P.; Scoletta, P.; Marangoni, E.; Ragazzi, R.; Azzena, G.; Frazzoli, E.; Di Luca, D.; Cassai, E.; Lombardi, G.; Cavallari, A.; Faenza, S.; Pasetto, A.; Girardis, M.; Jovine, E. and Pinna, A. D. (2002): Early experiences with a porcine hepatocyte-based bioartificial liver in acute hepatic failure patients, Int J Artif Organs, (vol. 25), No. 3, pp.192-202. Moza, A. K.; Mertsching, H.; Herden, T.; Bader, A. and Haverich, A. (2001): Heart valves from pigs and the porcine endogenous retrovirus: experimental and clinical data to assess the probability of porcine endogenous retrovirus infection in human subjects, J Thorac Cardiovasc Surg, (vol. 121), No. 4, pp.697-701. Mueller, N. J.; Barth, R. N.; Yamamoto, S.; Kitamura, H.; Patience, C.; Yamada, K.; Cooper, D. K.; Sachs, D. H.; Kaur, A. and Fishman, J. A. (2002): Activation of cytomegalovirus in pig-to-primate organ xenotransplantation, J Virol, (vol. 76), No. 10, pp.4734-40. Munk, C.; Brandt, S. M.; Lucero, G. and Landau, N. R. (2002): A dominant block to HIV-1 replication at reverse transcription in simian cells, Proc Natl Acad Sci U S A, (vol. 99), No. 21, pp.13843-8. Newgard, C. B.; Clark, S.; BeltrandelRio, H.; Hohmeier, H. E.; Quaade, C. and Normington, K. (1997): Engineered cell lines for insulin replacement in diabetes: current status and future prospects, Diabetologia, (vol. 40 Suppl 2), pp.S42-7. Nuffield Council on Bioethics 1996 Animal-to-human transplants: the ethics of xenotransplantation. Secondary Title: Nuffield Council on Bioethics

London, United Kingdom

Nyberg, S. L.; Hibbs, J. R.; Hardin, J. A.; Germer, J. J. and Persing, D. H. (1999): Transfer of porcine endogenous retrovirus across hollow fiber membranes: significance to a bioartificial liver, Transplantation, (vol. 67), No. 9, pp.1251-5. O'Connell, P. (2002): Pancreatic islet xenotransplantation, Xenotransplantation, (vol. 9), No. 6, pp.367-71. O'Rourke, L. G. (2000): Xenotransplantation, Brown, C. and Bolin, C., Eds, Emerging diseases of animals, pp. 59-84, American Society for Microbiology,

Washington, D.C.

. Oberholzer, J.; Triponez, F.; Mage, R.; Andereggen, E.; Buhler, L.; Cretin, N.; Fournier, B.; Goumaz, C.; Lou, J.; Philippe, J. and Morel, P. (2000): Human islet transplantation: lessons from 13 autologous and 13 allogeneic transplantations, Transplantation, (vol. 69), No. 6, pp.1115-23. Ogawa, H.; Kobayashi, T.; Yokoyama, I.; Nagatani, N.; Mizuno, M.; Yoshida, J.; Kadomatsu, K.; Muramatsu, H.; Nakao, A. and Muramatsu, T. (2002): Reduction of alpha-galactosyl xenoantigen by expression of endo-beta-galactosidase C in pig endothelial cells, Xenotransplantation, (vol. 9), No. 4, pp.290-6. Ogawa, Y.; Sagata, N.; Tsuzuku-Kawamura, J.; Onuma, M.; Izawa, H. and Ikawa, Y. (1985): Methylation pattern of the bovine leukemia provirus genome in bovine leukemic cells, Jpn J Cancer Res, (vol. 76), No. 1, pp.5-8. Oldmixon, B. A.; Wood, J. C.; Ericsson, T. A.; Wilson, C. A.; White-Scharf, M. E.; Andersson, G.; Greenstein, J. L.; Schuurman, H. J. and Patience, C. (2002): Porcine endogenous retrovirus transmission characteristics of an inbred herd of miniature swine, J Virol, (vol. 76), No. 6, pp.3045-8. Onion, D. and et al (2000): Xenotransplantation Subcommittee: Report of the Food and Drug Administration Subcommittee on Xenotransplantation: meeting of 13 January 2000, Center for Biologics and Evaluation and Research, Xenotransplantation, (vol. 7), pp.75-79. Osman, N.; McKenzie, I. F.; Ostenried, K.; Ioannou, Y. A.; Desnick, R. J. and Sandrin, M. S. (1997): Combined transgenic expression of alpha-galactosidase and alpha1,2-fucosyltransferase leads to optimal reduction in the major xenoepitope Galalpha(1,3)Gal, Proc Natl Acad Sci U S A, (vol. 94), No. 26, pp.14677-82. Paradis, K.; Langford, G.; Long, Z.; Heneine, W.; Sandstrom, P.; Switzer, W. M.; Chapman, L. E.; Lockey, C.; Onions, D. and Otto, E. (1999): Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group, Science, (vol. 285), No. 5431, pp.1236-41. Parker, W.; Bruno, D.; Holzknecht, Z. E. and Platt, J. L. (1994): Characterization and affinity isolation of xenoreactive human natural antibodies, J Immunol, (vol. 153), No. 8, pp.3791-803. Patience, C.; Patton, G. S.; Takeuchi, Y.; Weiss, R. A.; McClure, M. O.; Rydberg, L. and Breimer, M. E. (1998): No evidence of pig DNA or retroviral infection in patients with short-term extracorporeal connection to pig kidneys, Lancet, (vol. 352), No. 9129, pp.699-701. Patience, C.; Switzer, W. M.; Takeuchi, Y.; Griffiths, D. J.; Goward, M. E.; Heneine, W.; Stoye, J. P. and Weiss, R. A. (2001): Multiple groups of novel retroviral genomes in pigs and related species, J Virol, (vol. 75), No. 6, pp.2771-5. Patience, C.; Takeuchi, Y. and Weiss, R. A. (1997): Infection of human cells by an endogenous retrovirus of pigs, Nat Med, (vol. 3), No. 3, pp.282-6. Paton, N. I.; Leo, Y. S.; Zaki, S. R.; Auchus, A. P.; Lee, K. E.; Ling, A. E.; Chew, S. K.; Ang, B.; Rollin, P. E.; Umapathi, T.; Sng, I.; Lee, C. C.; Lim, E. and Ksiazek, T. G. (1999): Outbreak of Nipah-virus infection among abattoir workers in Singapore, Lancet, (vol. 354), No. 9186, pp.1253-6. Paul, P. S.; Halbur, P.; Janke, B.; Joo, H.; Nawagitgul, P.; Singh, J. and Sorden, S. (2003): Exogenous porcine viruses, Curr Top Microbiol Immunol, (vol. 278), pp.125-83. Phelps, C. J.; Koike, C.; Vaught, T. D.; Boone, J.; Wells, K. D.; Chen, S. H.; Ball, S.; Specht, S. M.; Polejaeva, I. A.; Monahan, J. A.; Jobst, P. M.; Sharma, S. B.; Lamborn, A. E.; Garst, A. S.; Moore, M.; Demetris, A. J.; Rudert, W. A.; Bottino, R.; Bertera, S.; Trucco, M.; Starzl, T. E.; Dai, Y. and Ayares, D. L. (2003): Production of alpha 1,3-galactosyltransferase-deficient pigs, Science, (vol. 299), No. 5605, pp.411-4. Pincus, T.; Hartley, J. W. and Rowe, W. P. (1971): A major genetic locus affecting resistance to infection with murine leukemia viruses. I. Tissue culture studies of naturally occurring viruses, J Exp Med, (vol. 133), No. 6, pp.1219-33. Pion, M.; Jordan, A.; Biancotto, A.; Dequiedt, F.; Gondois-Rey, F.; Rondeau, S.; Vigne, R.; Hejnar, J.; Verdin, E. and Hirsch, I. (2003): Transcriptional suppression of in vitro-integrated human immunodeficiency virus type 1 does not correlate with proviral DNA methylation, J Virol, (vol. 77), No. 7, pp.4025-32. Pirtle, E. C. and Woods, L. K. (1968): Cytogenetic alterations in swine kidney cells persistently infected with hog cholera virus and propagated with and without antiserum in the medium, Am J Vet Res, (vol. 29), No. 1, pp.153-64. Pitkin, Z. and Mullon, C. (1999): Evidence of absence of porcine endogenous retrovirus (PERV) infection in patients treated with a bioartificial liver support system, Artif Organs, (vol. 23), No. 9, pp.829-33. Powell, S. K.; Gates, M. E.; Langford, G.; Gu, M. L.; Lockey, C.; Long, Z. and Otto, E. (2000): Antiretroviral agents inhibit infection of human cells by porcine endogenous retroviruses, Antimicrob Agents Chemother, (vol. 44), No. 12, pp.3432-3. Pryciak, P. M. and Varmus, H. E. (1992): Fv-1 restriction and its effects on murine leukemia virus integration in vivo and in vitro, J Virol, (vol. 66), No. 10, pp.5959-66. Qari, S. H.; Magre, S.; Garcia-Lerma, J. G.; Hussain, A. I.; Takeuchi, Y.; Patience, C.; Weiss, R. A. and Heneine, W. (2001): Susceptibility of the porcine endogenous retrovirus to reverse transcriptase and protease inhibitors, J Virol, (vol. 75), No. 2, pp.1048-53. Ramiya, V. K.; Maraist, M.; Arfors, K. E.; Schatz, D. A.; Peck, A. B. and Cornelius, J. G. (2000): Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells, Nat Med, (vol. 6), No. 3, pp.278-82. Ramsoondar, J. J.; Machaty, Z.; Costa, C.; Williams, B. L.; Fodor, W. L. and Bondioli, K. R. (2003): Production of alpha 1,3-galactosyltransferase-knockout cloned pigs expressing human alpha 1,2-fucosylosyltransferase, Biol Reprod, (vol. 69), No. 2, pp.437-45. Reddacliff, L. A.; Kirkland, P. D.; Hartley, W. J. and Reece, R. L. (1997): Encephalomyocarditis virus infections in an Australian zoo, J Zoo Wildl Med, (vol. 28), No. 2, pp.153-7. Riordan, S. M. and Williams, R. (1999): Extracorporeal support and hepatocyte transplantation in acute liver failure and cirrhosis, J Gastroenterol Hepatol, (vol. 14), No. 8, pp.757-70. Ritzhaupt, A.; Van Der Laan, L. J.; Salomon, D. R. and Wilson, C. A. (2002): Porcine endogenous retrovirus infects but does not replicate in nonhuman primate primary cells and cell lines, J Virol, (vol. 76), No. 22, pp.11312-20. Rother, R. P.; Fodor, W. L.; Springhorn, J. P.; Birks, C. W.; Setter, E.; Sandrin, M. S.; Squinto, S. P. and Rollins, S. A. (1995): A novel mechanism of retrovirus inactivation in human serum mediated by anti-alpha-galactosyl natural antibody, J Exp Med, (vol. 182), No. 5, pp.1345-55. Rupasinghe, V.; Iwatsuki-Horimoto, K.; Sugii, S. and Horimoto, T. (2001): Identification of the porcine cytomegalovirus major capsid protein gene, J Vet Med Sci, (vol. 63), No. 6, pp.609-18. Sachs, D. H. (1994): The pig as a potential xenograft donor, Vet Immunol Immunopathol, (vol. 43), No. 1-3, pp.185-91. Sachs, D. H.; Sykes, M.; Robson, S. C. and Cooper, D. K. (2001): Xenotransplantation, Adv Immunol, (vol. 79), pp.129-223. Santos, N.; Lima, R. C.; Nozawa, C. M.; Linhares, R. E. and Gouvea, V. (1999): Detection of porcine rotavirus type G9 and of a mixture of types G1 and G5 associated with Wa-like VP4 specificity: evidence for natural human-porcine genetic reassortment, J Clin Microbiol, (vol. 37), No. 8, pp.2734-6. Sauer, I. M.; Kardassis, D.; Zeillinger, K.; Pascher, A.; Gruenwald, A.; Pless, G.; Irgang, M.; Kraemer, M.; Puhl, G.; Frank, J.; Muller, A. R.; Steinmuller, T.; Denner, J.; Neuhaus, P. and Gerlach, J. C. (2003): Clinical extracorporeal hybrid liver support--phase I study with primary porcine liver cells, Xenotransplantation, (vol. 10), No. 5, pp.460-9. Sayre, K. R.; Dodd, R. Y.; Tegtmeier, G.; Layug, L.; Alexander, S. S. and Busch, M. P. (1996): False-positive human immunodeficiency virus type 1 western blot tests in noninfected blood donors, Transfusion, (vol. 36), No. 1, pp.45-52. Scheef, G.; Fischer, N.; Flory, E.; Schmitt, I. and Tonjes, R. R. (2002): Transcriptional regulation of porcine endogenous retroviruses released from porcine and infected human cells by heterotrimeric protein complex NF-Y and impact of immunosuppressive drugs, J Virol, (vol. 76), No. 24, pp.12553-63. Scheef, G.; Fischer, N.; Krach, U. and Tonjes, R. R. (2001): The number of a U3 repeat box acting as an enhancer in long terminal repeats of polytropic replication-competent porcine endogenous retroviruses dynamically fluctuates during serial virus passages in human cells, J Virol, (vol. 75), No. 15, pp.6933-40. Schmoeckel, M.; Bhatti, F. N.; Zaidi, A.; Cozzi, E.; Waterworth, P. D.; Tolan, M. J.; Pino-Chavez, G.; Goddard, M.; Warner, R. G.; Langford, G. A.; Dunning, J. J.; Wallwork, J. and White, D. J. (1998): Orthotopic heart transplantation in a transgenic pig-to-primate model, Transplantation, (vol. 65), No. 12, pp.1570-7. Schumacher, J. M.; Ellias, S. A.; Palmer, E. P.; Kott, H. S.; Dinsmore, J.; Dempsey, P. K.; Fischman, A. J.; Thomas, C.; Feldman, R. G.; Kassissieh, S.; Raineri, R.; Manhart, C.; Penney, D.; Fink, J. S. and Isacson, O. (2000): Transplantation of embryonic porcine mesencephalic tissue in patients with PD, Neurology, (vol. 54), No. 5, pp.1042-50. Schuurman, H. J.; Pino-Chavez, G.; Phillips, M. J.; Thomas, L.; White, D. J. and Cozzi, E. (2002): Incidence of hyperacute rejection in pig-to-primate transplantation using organs from hDAF-transgenic donors, Transplantation, (vol. 73), No. 7, pp.1146-51. Schweizer, M.; Falcone, V.; Gange, J.; Turek, R. and Neumann-Haefelin, D. (1997): Simian foamy virus isolated from an accidentally infected human individual, J Virol, (vol. 71), No. 6, pp.4821-4. Scobie, L.; Taylor, S.; Wood, J. C.; Suling, K. M.; Quinn, G.; Meikle, S.; Patience, C.; Schuurman, H. J. and Onions, D. E. (2004): Absence of replication-competent human-tropic porcine endogenous retroviruses in the germ line DNA of inbred miniature Swine, J Virol, (vol. 78), No. 5, pp.2502-9. Sepp, A.; Farrar, C. A.; Dorling, T.; Cairns, T.; George, A. J. and Lechler, R. I. (1999): Inhibition of expression of the Galalpha1-3Gal epitope on porcine cells using an intracellular single-chain antibody directed against alpha1,3galactosyltransferase, J Immunol Methods, (vol. 231), No. 1-2, pp.191-205. Shafren, D. R.; Bates, R. C.; Agrez, M. V.; Herd, R. L.; Burns, G. F. and Barry, R. D. (1995): Coxsackieviruses B1, B3, and B5 use decay accelerating factor as a receptor for cell attachment, J Virol, (vol. 69), No. 6, pp.3873-7. Shapiro, A. M.; Lakey, J. R.; Ryan, E. A.; Korbutt, G. S.; Toth, E.; Warnock, G. L.; Kneteman, N. M. and Rajotte, R. V. (2000): Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen, N Engl J Med, (vol. 343), No. 4, pp.230-8. Sharma, A.; Okabe, J.; Birch, P.; McClellan, S. B.; Martin, M. J.; Platt, J. L. and Logan, J. S. (1996): Reduction in the level of Gal(alpha1,3)Gal in transgenic mice and pigs by the expression of an alpha(1,2)fucosyltransferase, Proc Natl Acad Sci U S A, (vol. 93), No. 14, pp.7190-5. Shirali, G. S.; Ni, J.; Chinnock, R. E.; Johnston, J. K.; Rosenthal, G. L.; Bowles, N. E. and Towbin, J. A. (2001): Association of viral genome with graft loss in children after cardiac transplantation, N Engl J Med, (vol. 344), No. 20, pp.1498-503. Smit, A. F. (1999): Interspersed repeats and other mementos of transposable elements in mammalian genomes, Curr Opin Genet Dev, (vol. 9), No. 6, pp.657-63. Smith, C. E.; Simpson, D. I.; Bowen, E. T. and Zlotnik, I. (1967): Fatal human disease from vervet monkeys, Lancet, (vol. 2), No. 7526, pp.1119-21. Soin, B.; Smith, K. G.; Zaidi, A.; Cozzi, E.; Bradley, J. R.; Ostlie, D. J.; Lockhart, A.; White, D. J. and Friend, P. J. (2001): Physiological aspects of pig-to-primate renal xenotransplantation, Kidney Int, (vol. 60), No. 4, pp.1592-7. Sorden, S. D.; Harms, P. A.; Nawagitgul, P.; Cavanaugh, D. and Paul, P. S. (1999): Development of a polyclonal-antibody-based immunohistochemical method for the detection of type 2 porcine circovirus in formalin-fixed, paraffin-embedded tissue, J Vet Diagn Invest, (vol. 11), No. 6, pp.528-30. Specke, V.; Plesker, R.; Coulibaly, C.; Boller, K. and Denner, J. (2002): Productive infection of a mink cell line with porcine endogenous retroviruses (PERVs) but lack of transmission to minks in vivo, Arch Virol, (vol. 147), No. 2, pp.305-19. Specke, V.; Rubant, S. and Denner, J. (2001): Productive infection of human primary cells and cell lines with porcine endogenous retroviruses, Virology, (vol. 285), No. 2, pp.177-80. Specke, V.; Schuurman, H. J.; Plesker, R.; Coulibaly, C.; Ozel, M.; Langford, G.; Kurth, R. and Denner, J. (2002): Virus safety in xenotransplantation: first exploratory in vivo studies in small laboratory animals and non-human primates, Transpl Immunol, (vol. 9), No. 2-4, pp.281-8. Specke, V.; Tacke, S. J.; Boller, K.; Schwendemann, J. and Denner, J. (2001): Porcine endogenous retroviruses: in vitro host range and attempts to establish small animal models, J Gen Virol, (vol. 82), No. Pt 4, pp.837-44. Stephan, O.; Schwendemann, J.; Specke, V.; Tacke, S. J.; Boller, K. and Denner, J. (2001): Porcine endogenous retroviruses (PERVs): generation of specific antibodies, development of an immunoperoxidase assay (IPA) and inhibition by AZT, Xenotransplantation, (vol. 8), No. 4, pp.310-6. Storck, M.; Abendroth, D.; Prestel, R.; Pino-Chavez, G.; Muller-Hoker, J.; White, D. J. and Hammer, C. (1997): Morphology of hDAF (CD55) transgenic pig kidneys following ex-vivo hemoperfusion with human blood, Transplantation, (vol. 63), No. 2, pp.304-10. Stremlau, M.; Owens, C. M.; Perron, M. J.; Kiessling, M.; Autissier, P. and Sodroski, J. (2004): The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys, Nature, (vol. 427), No. 6977, pp.848-53. Suzuka, I.; Sekiguchi, K. and Kodama, M. (1985): Some characteristics of a porcine retrovirus from a cell line derived from swine malignant lymphomas, FEBS Lett, (vol. 183), No. 1, pp.124-8. Suzuka, I.; Shimizu, N.; Sekiguchi, K.; Hoshino, H.; Kodama, M. and Shimotohno, K. (1986): Molecular cloning of unintegrated closed circular DNA of porcine retrovirus, FEBS Lett, (vol. 198), No. 2, pp.339-43. Swanstrom, R. and Vogt, P.K. (1990): Retroviruses: Strategies of replication., Swanstrom, R, Vogt, PK, Ed, Current Topics in Microbiology and Immunology (vol. 157), Springer-Verlag,

Heidelberg

. Switzer, W. M.; Michler, R. E.; Shanmugam, V.; Matthews, A.; Hussain, A. I.; Wright, A.; Sandstrom, P.; Chapman, L. E.; Weber, C.; Safley, S.; Denny, R. R.; Navarro, A.; Evans, V.; Norin, A. J.; Kwiatkowski, P. and Heneine, W. (2001): Lack of cross-species transmission of porcine endogenous retrovirus infection to nonhuman primate recipients of porcine cells, tissues, or organs, Transplantation, (vol. 71), No. 7, pp.959-65. Switzer, W. M.; Shanmugam, V.; Chapman, L. E. and Heneine, W. (1999): Polymerase chain reaction assays for the diagnosis of infection with the porcine endogenous retrovirus and the detection of pig cells in human and nonhuman recipients of pig xenografts, Transplantation, (vol. 68), p.183. Tacke, S. J.; Bodusch, K.; Berg, A. and Denner, J. (2001): Sensitive and specific immunological detection methods for porcine endogenous retroviruses applicable to experimental and clinical xenotransplantation, Xenotransplantation, (vol. 8), No. 2, pp.125-35. Tacke, S. J.; Kurth, R. and Denner, J. (2000): Porcine endogenous retroviruses inhibit human immune cell function: risk for xenotransplantation?, Virology, (vol. 268), No. 1, pp.87-93. Tacke, S. J.; Specke, V. and Denner, J. (2003): Differences in release and determination of subtype of porcine endogenous retroviruses produced by stimulated normal pig blood cells, Intervirology, (vol. 46), No. 1, pp.17-24. Tajima, S.; Takahashi, M.; Takeshima, S. N.; Konnai, S.; Yin, S. A.; Watarai, S.; Tanaka, Y.; Onuma, M.; Okada, K. and Aida, Y. (2003): A mutant form of the tax protein of bovine leukemia virus (BLV), with enhanced transactivation activity, increases expression and propagation of BLV in vitro but not in vivo, J Virol, (vol. 77), No. 3, pp.1894-903. Takahashi, M.; Ishikura, H.; Takahashi, C.; Nakajima, Y.; Matsushita, M.; Matsue, H.; Sato, K.; Noto, H.; Taguchi, K. and et al. (1993): Immunologic considerations in the use of cultured porcine hepatocytes as a hybrid artificial liver. Anti-porcine hepatocyte human serum, Asaio J, (vol. 39), No. 3, pp.M242-6. Takefman, D. M.; Spear, G. T.; Saifuddin, M. and Wilson, C. A. (2002): Human CD59 incorporation into porcine endogenous retrovirus particles: implications for the use of transgenic pigs for xenotransplantation, J Virol, (vol. 76), No. 4, pp.1999-2002. Takeuchi, Y.; Patience, C.; Magre, S.; Weiss, R. A.; Banerjee, P. T.; Le Tissier, P. and Stoye, J. P. (1998): Host range and interference studies of three classes of pig endogenous retrovirus, J Virol, (vol. 72), No. 12, pp.9986-91. Takeuchi, Y.; Porter, C. D.; Strahan, K. M.; Preece, A. F.; Gustafsson, K.; Cosset, F. L.; Weiss, R. A. and Collins, M. K. (1996): Sensitization of cells and retroviruses to human serum by (alpha 1-3) galactosyltransferase, Nature, (vol. 379), No. 6560, pp.85-8. Tanczos, E.; Horch, R. E.; Bannasch, H.; Andree, C.; Walgenbach, K. J.; Voigt, M. and Stark, G. B. (1999): [Keratinocyte transplantation and tissue engineering. New approaches in treatment of chronic wounds], Zentralbl Chir, (vol. 124 Suppl 1), pp.81-6. Tanemura, M.; Ogawa, H.; Yin, D. P.; Chen, Z. C.; DiSesa, V. J. and Galili, U. (2002): Elimination of anti-Gal B cells by alpha-Gal ricin1, Transplantation, (vol. 73), No. 12, pp.1859-68. Taubenberger, J. K.; Reid, A. H.; Krafft, A. E.; Bijwaard, K. E. and Fanning, T. G. (1997): Initial genetic characterization of the 1918 "Spanish" influenza virus, Science, (vol. 275), No. 5307, pp.1793-6. Todaro, G. J.; Benveniste, R. E.; Lieber, M. M. and Sherr, C. J. (1974): Characterization of a type C virus released from the porcine cell line PK(15), Virology, (vol. 58), No. 1, pp.65-74. Todaro, G. J. and Green, H. (1963): Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines, J Cell Biol, (vol. 17), pp.299-313. Todaro, G. J.; Sherr, C. J.; Benveniste, R. E.; Lieber, M. M. and Melnick, J. L. (1974): Type C viruses of baboons: isolation from normal cell cultures, Cell, (vol. 2), No. 1, pp.55-61. Towers, G.; Bock, M.; Martin, S.; Takeuchi, Y.; Stoye, J. P. and Danos, O. (2000): A conserved mechanism of retrovirus restriction in mammals, Proc Natl Acad Sci U S A, (vol. 97), No. 22, pp.12295-9. Tucker, A.; Belcher, C.; Moloo, B.; Bell, J.; Mazzulli, T.; Humar, A.; Hughes, A.; McArdle, P. and Talbot, A. (2002): The production of transgenic pigs for potential use in clinical xenotransplantation: microbiological evaluation, Xenotransplantation, (vol. 9), No. 3, pp.191-202. Tucker, A. W.; Galbraith, D.; McEwan, P. and Onions, D. (1999): Evaluation of porcine cytomegalovirus as a potential zoonotic agent in xenotransplantation, Transplant Proc, (vol. 31), No. 1-2, p.915. Tucker, A. W.; McNeilly, F.; Meehan, B.; Galbraith, D.; McArdle, P. D.; Allan, G. and Patience, C. (2003): Methods for the exclusion of circoviruses and gammaherpesviruses from pigs, Xenotransplantation, (vol. 10), No. 4, pp.343-8. Valdes, R. (2002): Xenotransplantation trials, Lancet, (vol. 359), No. 9325, p.2281. van der Kuyl, A. C.; Dekker, J. T. and Goudsmit, J. (1996): Baboon endogenous virus evolution and ecology, Trends Microbiol, (vol. 4), No. 11, pp.455-9. van der Laan, L. J.; Lockey, C.; Griffeth, B. C.; Frasier, F. S.; Wilson, C. A.; Onions, D. E.; Hering, B. J.; Long, Z.; Otto, E.; Torbett, B. E. and Salomon, D. R. (2000): Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice, Nature, (vol. 407), No. 6800, pp.90-4. Vanhove, B.; Charreau, B.; Cassard, A.; Pourcel, C. and Soulillou, J. P. (1998): Intracellular expression in pig cells of anti-alpha1,3galactosyltransferase single-chain FV antibodies reduces Gal alpha1,3Gal expression and inhibits cytotoxicity mediated by anti-Gal xenoantibodies, Transplantation, (vol. 66), No. 11, pp.1477-85. Weiss, R. A. (1998): Transgenic pigs and virus adaptation, Nature, (vol. 391), No. 6665, pp.327-8. Wells, D. L.; Hopfensperger, D. J.; Arden, N. H.; Harmon, M. W.; Davis, J. P.; Tipple, M. A. and Schonberger, L. B. (1991): Swine influenza virus infections. Transmission from ill pigs to humans at a Wisconsin agricultural fair and subsequent probable person-to-person transmission, Jama, (vol. 265), No. 4, pp.478-81. Welsh, R. M.; O'Donnell, C. L.; Reed, D. J. and Rother, R. P. (1998): Evaluation of the Galalpha1-3Gal epitope as a host modification factor eliciting natural humoral immunity to enveloped viruses, J Virol, (vol. 72), No. 6, pp.4650-6. Wilson, C. A.; Wong, S.; Muller, J.; Davidson, C. E.; Rose, T. M. and Burd, P. (1998): Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells, J Virol, (vol. 72), No. 4, pp.3082-7. Wilson, C. A.; Wong, S.; VanBrocklin, M. and Federspiel, M. J. (2000): Extended analysis of the in vitro tropism of porcine endogenous retrovirus, J Virol, (vol. 74), No. 1, pp.49-56. Wolgamot, G.; Bonham, L. and Miller, A. D. (1998): Sequence analysis of Mus dunni endogenous virus reveals a hybrid VL30/gibbon ape leukemia virus-like structure and a distinct envelope, J Virol, (vol. 72), No. 9, pp.7459-66. Wood, J. C.; Quinn, G.; Suling, K. M.; Oldmixon, B. A.; Van Tine, B. A.; Cina, R.; Arn, S.; Huang, C. A.; Scobie, L.; Onions, D. E.; Sachs, D. H.; Schuurman, H. J.; Fishman, J. A. and Patience, C. (2004): Identification of exogenous forms of human-tropic porcine endogenous retrovirus in miniature Swine, J Virol, (vol. 78), No. 5, pp.2494-501. Xu, Y.; Lorf, T.; Sablinski, T.; Gianello, P.; Bailin, M.; Monroy, R.; Kozlowski, T.; Awwad, M.; Cooper, D. K. and Sachs, D. H. (1998): Removal of anti-porcine natural antibodies from human and nonhuman primate plasma in vitro and in vivo by a Galalpha1-3Galbeta1-4betaGlc-X immunoaffinity column, Transplantation, (vol. 65), No. 2, pp.172-9. Yoder, J. A.; Walsh, C. P. and Bestor, T. H. (1997): Cytosine methylation and the ecology of intragenomic parasites, Trends Genet, (vol. 13), No. 8, pp.335-40. Zhang, W. J.; Laue, C.; Hyder, A. and Schrezenmeir, J. (2001): Purity of alginate affects the viability and fibrotic overgrowth of encapsulated porcine islet xenografts, Transplant Proc, (vol. 33), No. 7-8, pp.3517-9.