Advances in solid organ transplantation and a chronic shortage of suitable organ donors have made xenotransplantation an attractive alternative to the use of human allografts. However, the potential for introduction of a new group of infectious diseases from donor animals into the human population is a concern with the use of these methods.
The term applied to the natural acquisition by humans of infectious agents carried by other species is zoonosis. The transplantation of infection from nonhuman species into humans is best termed “direct zoonosis” or “xenosis.”
Nonhuman primates and swine have been considered the main potential sources of organs for xenotransplantation (Niekrasz et al. (1992) Transplant Proc 24:625; Starzl et al. (1993) Lancet 341:65; Murphy et al. (1970) Trans Proc 4:546; Brede and Murphy (1972) Primates Med 7:18; Cooper et al. In Xenotransplantation: The Transplantation of Organs and Tissues between Species, eds. Cooper et al. (1991) p. 457; R Y Calne (1970) Transplant Proc 2:550; H. Auchincloss, Jr. (1988) Transplantation 46:1; and Chiche et al. (1993) Transplantation 6:1418). The infectious disease issues for primates and swine are similar to those of human donors. The prevention of infection depends on the ability to predict, to recognize, and to prevent common infections in the immunocompromised transplantation recipient (Rubin et al. (1993) Antimicrob Agents Chemother 37:619). Because of the potential carriage by nonhuman primates of pathogens easily adopted to humans, ethical concerns, and the cost of maintaining large colonies of primates, other species have received consideration as organ donors (Brede and Murphy (1972) Primates Med 7:18; Van Der Riet et al. (1987) Transplant Proc 19:4069; Katler In Xenotransplantation: The Transplantation of Organs and Tissues between Species, eds. Cooper et al. (1991) p. 457; Metzger et al. (1981) J Immunol 127:769; McClure et al. (1987) Nature 330:487; Letvin et al. (1987) J Infect Dis 156:406; Castro et al. (1991) Virology 184:219; Benveniste and Todaro (1973) Proc Natl Acad Sci USA 70:3316; and Teich, in RNA Tumor viruses, eds. Weiss et. al. (1985) p. 25). The economic importance of swine and experience in studies of transplantation in the miniature swine model have allowed some of the potential pathogens associated with these animals to be defined (Niekrasz et al. (1992) Transplant Proc 24:625; Cooper et al. In Xenotransplantation: The Transplantation of Organs and Tissues between Species, eds. Cooper et al. (1991) p. 457; and Leman et al. (1992) Diseases of Swine, 7th ed. Ames, Iowa:Iowa State University). Miniature swine have received consideration as organ donors because of a number of features of the species. The structure and function of the main pig organs are comparable to those of man. Swine attain body weights and organ sizes adequate to the provision of organs for human use. Lastly, veterinarians and commercial breeders have developed approaches to creation of specific-pathogen-free (SPF) swine with the ability to eliminate known pathogens from breeding colonies (Alexander et al. (1980) Proc 6th Int Congr Pig Vet Soc, Copenhagen; Betts (1961) Vet Rec 73:1349; Betts et al. (1960) Vet Rec 72:461; Caldwell et al. (1959) J Am Vet Med Assoc 135:504; and Yong (1964) Adv Vet Sci 9:61).
Concern exists over the transfer of porcine retroviruses by xenotransplantation (Smith (1993) N Engl J Med 328:141). Many of the unique properties of the retroviruses are due to the synthesis of a complementary DNA copy from the RNA template (by reverse transcriptase), and integration of this DNA into the host genome. The integrated retroviral copy (which is referred to as an endogenous copy or “provirus”) can be transmitted via the germ line.