Possible Viral Zoonoses in Xenotransplantation

Pig-to-human xenotransplantation has been proposed as a possible solution to the world shortage of organ donors. Additionally, cell/tissue xenotransplantation shows promise in the treatment of patients with diabetes, neuronal and eye diseases. At present, barriers to xenotransplantation still include graft rejection, physiological compatibility issues and the threat posed by zoonoses. In this article, the current information from recent publications in the field of porcine zoonoses and xenotransplantation is presented. Pathogens of concern including herpesviruses, endogenous retroviruses and hepatitis E virus are known and risk reduction measures against these in xenotranplantation settings are described. Unidentified pathogens pose a separate risk that may not be identified until clinical trials take place and risks vary depending on the diseases, operation practices and graft production processes including geographical factors. Currently, a number of clinical trials are underway using encapsulated porcine islets, which may alter the perceived risks of pathogen transfer. Key Concepts: Prevention of pathogen transfer in xenotransplantation. The risk of porcine zoonoses is one that should be minimised before xenotransplantation is carried out in human trials. The use of techniques such as encapsulation in cellular xenotransplantation could be used to potentially protect against pathogen transfer. Donor animals used in xenotransplantation should come from specific pathogen-free herds which have been screened and tested negative for known and potentially zoonotic viruses, such as Swine influenza, hepatitis E, porcine cytomegalovirus and porcine lymphotropic viruses. Porcine endogenous retroviruses cannot be eliminated from donor herds and although their zoonotic potential remains unknown, steps should be taken to minimise the possibility of zoonoses by selecting donor pigs with low PERV copy number and absence of known dangerous PERV subtype and loci. The possibility of unknown zoonotic viruses emerging poses a constant threat. To counteract this a high surveillance and investigatory approach is required, using the most advanced molecular techniques available. Keywords: xenotransplantation; zoonosis; virus; PERV; herpesvirus; unknown viruses; safety