Reappraisal of biosafety risks posed by PERVs in xenotransplantation.

Donor materials of porcine origin could potentially provide an alternative source of cells, tissues or whole organs for transplantation to humans, but is hampered by the health risk posed by infection with porcine viruses. Although pigs can be bred in such a way that all known exogenous microorganisms are eliminated, this is not feasible for all endogenous pathogens, such as the porcine endogenous retroviruses (PERVs) which are present in the germline of pigs as proviruses. Upon transplantation, PERV proviruses would be transferred to the human recipient along with the xenograft. If xenotransplantation stimulates or facilitates replication of PERVs in the new hosts, a risk exists for adaptation of the virus to humans and subsequent spread of these viruses. In a worst-case scenario, this might result in the emergence of a new viral disease. Although the concerns for disease potential of PERVs are easing, only limited pre-clinical and clinical data are available. Small-scale, well-designed and carefully controlled clinical trials would provide more evidence on the safety of this approach and allow a better appreciation of the risks involved. It is therefore important to have a framework of protective measures and monitoring protocols in place to facilitate such initially small scale clinical trials. This framework will raise ethical and social considerations regarding acceptability.