This research career award is designed to provide the candidate with research experience in xenotransplantation biology and porcine animal model of infectious diseases, with the long-term objective of establishing a research program in xenozoonosis. The candidate has research experience in cellular and molecular virology and the mouse animal model and he has recently taken a faculty position at the University of Minnesota, which is renowned for research in the fields of transplantation and pig diseases. The research project will investigate the risk posed by persistent porcine viruses, which may escape detection by standard screening methods to become pathogenic in humans following xenotransplatation. The experiments will utilize porcine encephalomyocarditis virus (EMCV), which has been shown to cause-species infection, to evaluate the risk of human infection after transplantation of pig tissues by examining various pigs tissues/organs using sensitive molecular techniques to determine where the virus persists. Subsequently, the applicants will transplant chronically EMCV-infected porcine tissues into SCID (severe combined immunodeficient) mice reconstituted with human peripheral blood lymphocytes followed by immunosuppressive treatment (hu-PBL-ISCID), in order to determine the risk of such tissues transmitting disease. The hu-PBL-ISCID mice will serve as a model of suppressed immune system in transplant patients. This training program will also require the candidate to observe and assist in monkey-to-monkey (allo-) and pig-to-monkey (xeno-) transplantations in an established transplantation laboratory. The long-term goal is to transplant pig organs/tissues containing persistent porcine virus into primates in order to determine the risk of disease.
