Xenozoonosis in Xenotransplantation: Clinical Challenges

Preclinical and clinical xenotransplantation trials performed until now have clearly demonstrated that the outcomes depend significantly on the prevention of xenozoonoses. In some preclinical trials where pig kidneys and hearts were transplanted into different non-human primates (marmosets, baboons, rhesus and cynomolgus monkeys) transmission of pig viruses was observed. Specifically, porcine cytomegalovirus (PCVM), a porcine roseolovirus (PRV), was transmitted causing a significant reduction of the survival time of the transplant. The official name of the virus is suid herpesvirus 2 (SuHV-2). Furthermore, porcine circovirus type 3 (PCV3) was also transmitted in preclinical trials. In this case no clinical signs were observed. In over 200 human patients receiving different pig materials including islet cells, nerve cells, skin as well as in ex vivo perfusions of pig organs, no porcine endogenous retroviruses (PERVs), which are integrated in the genome of all pigs, could establish itself in the new host. However, the presence of other viruses had not been analyzed and the survival time of the transplants was short. In clinical trials encapsulated pig islet cells from Auckland Island donor pigs were transplanted into diabetic humans in New Zealand and Argentina. The donor animals were microbiologically clean and well characterized, 14 viruses were found absent in the Auckland Island pigs and none of these viruses including PERV were transmitted to the recipients. In the first transplantation of a heart from a cloned genetically modified pig into a patient in Baltimore, PCMV/PRV was transmitted, contributing among other factors to the death of patient. The results underline that donor animals must be well characterized using sensitive and specific detection systems for porcine viruses.