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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01HL004369-03
Application #
6526575
Study Section
Special Emphasis Panel (ZHL1-CSR-C (F1))
Program Officer
Commarato, Michael
Project Start
2000-09-01
Project End
2004-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
3
Fiscal Year
2002
Total Cost
$142,044
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Myers, Suzanne E; LaRue, Rebecca; Shaw, Daniel P et al. (2009) Pathogenesis of coxsackievirus-B5 acquired from intra-renal porcine islet cell xenografts in diabetic mice. Xenotransplantation 16:91-8
Brewer, Laurie; LaRue, Rebecca; Hering, Bernhard et al. (2004) Transplanting encephalomyocarditis virus-infected porcine islet cells reverses diabetes in recipient mice but also transmits the virus. Xenotransplantation 11:160-70
Myers, Suzanne E; Brewer, Laurie; Shaw, Daniel P et al. (2004) Prevalent human coxsackie B-5 virus infects porcine islet cells primarily using the coxsackie-adenovirus receptor. Xenotransplantation 11:536-46
LaRue, Rebecca; Myers, Suzanne; Brewer, Laurie et al. (2003) A wild-type porcine encephalomyocarditis virus containing a short poly(C) tract is pathogenic to mice, pigs, and cynomolgus macaques. J Virol 77:9136-46
Brewer, Laurie; Brown, Corrie; Murtaugh, Michael P et al. (2003) Transmission of porcine encephalomyocarditis virus (EMCV) to mice by transplanting EMCV-infected pig tissues. Xenotransplantation 10:569-76
Brewer, L A; Lwamba, H C; Murtaugh, M P et al. (2001) Porcine encephalomyocarditis virus persists in pig myocardium and infects human myocardial cells. J Virol 75:11621-9