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Quartal 1999
Immunosuppression by Retroviruses:
Implications for Xenotransplantation The transplantation of organs from non-humans to humans allows for the possibility that endogenous retroviruses present in the genome of the donor animals may be expressed as viral particles and may be transmitted. Potential candidates for organ donors are baboons and pigs. Both, baboons and pigs, express endogenous retroviruses, which are able to infect human cells. The baboon endogenous retrovirus (BaEV) and the porcine endogenous retroviruses (PERVs) are closely related to retroviruses, which induce leukemias and immune deficiencies in mice, cats and gibbon apes. Most, if not all retroviruses, induce in the infected host an immunosuppression, the severity of which depends largely on the virus load. A pronounced immunosuppression is induced by human and simian immunodeficiency viruses (HIV and SIV), ultimately leading to AIDS. HIV originated by trans-species transmission from primates. SIVs, which are apathogenic in their natural hosts, are now highly pathogenic for man. We have shown that expression of PERVs can be induced by immune stimulation of lymphocytes from different pig strains (Yucatan Micropig, German landrace). Therefore, lymphocytes transmitted as part of the transplant may be stimulated by human cells to produce PERVs. We demonstrated that purified PERVs and BaEV inhibit the mitogen-triggered proliferation of human peripheral blood mononuclear cells (PBMC). In previous experiments we had also been able to show that a synthetic peptide corresponding to a highly conserved region of the transmembrane envelope protein gp41 of HIV-1 inhibits human T and B lymphocytes. In the transmembrane envelope proteins of BaEV and PERV a related domain has been identified. Synthetic peptides corresponding to the immunosuppressive domains of BaEV, PERV-A and PERV-B were also immunosuppressive. In analogy to HIV and SIV, high titer virus replication might cause immunodeficiency in the human transplant recipient. Three additional points have to be considered: First, human anti-complement proteins produced by transgenic animals will also protect the virus. Secondly, medical immunosuppression is used to prevent transplant rejection, and thirdly, the virus may be transmitted to other humans and thus increase its pathogenic potential. In vitro and in vivo models should be used to evaluate the potential risk originating from the transmission of endogenous retroviruses during xenotransplantation.
Key words: Xenotransplantation, endogenous retroviruses, immunodeficiency, diagnostics, HIV
Dr. J. Denner
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