Xenotransplantation and the potential risk of xenogeneic transmission of porcine viruses

The clinical success of allotransplantation and the shortage of donor organs have led to a proposal for the use of animal organs as alternative therapeutic materials for humans. In that regard, swine are preferable to non-human primates as a source of donor organs. While applications for clinical trials for xenotransplantation have not yet been received in Canada, several trials have already been authorized in the United States. A major concern, however, is the potential for xenogeneic transmission of viruses from animals to humans via organ, tissue, or cellular transplantation or via ex vivo exposure of humans to porcine biologic materials. Xenotransplantation allows viruses to bypass the normal immunological defense mechanisms of the recipient. Furthermore, the use of immunosuppressive drugs following transplantation may facilitate the xenogeneic transmission of zoonotic agents. Of porcine viruses, swine hepatitis E virus does not cause any clinical symptoms in the natural host but is a likely zoonotic agent that can infect humans and cause hepatitis. Porcine circovirus type 1 is prevalent in swine populations with no known association with clinical disease, while circovirus type 2 causes post-weaning multi-systemic wasting syndrome. Porcine endogenous retrovirus is integrated into the host chromosomes while porcine cytomegalovirus undergoes latent infection. Two additional porcine herpesviruses have recently been identified in swine and have been named porcine lymphotrophic herpesviruses. These herpesviruses can potentially become reactivated in human recipients after xenotransplantation. All in all, there are a number of viruses in swine that are of primary concern to screen and eliminate from xenotransplantation protocols. Epidemiology and the current knowledge on xenogeneic risk of these viruses are discussed.