RISK OF PORCINE PICORNAVIRUS IN XENOTRANSPLATATION

描述 (根据申请者的摘要改编)本研究事业奖旨在 为应聘者提供异种移植生物学方面的研究经验 和猪的传染病动物模型，具有长远的目标 建立一个关于异种寄生虫病的研究项目。候选人有 细胞和分子病毒学与小鼠动物的研究经验 模特，他最近在加州大学担任教职 明尼苏达州，它以移植和研究领域而闻名 猪病。该研究项目将调查 持久性猪病毒，可能逃脱标准筛查的检测 方法异种移植后在人体内致病。这个 实验将利用猪脑心肌炎病毒(EMCV)，它具有 被证明是导致物种感染的原因，以评估人类感染的风险 猪组织移植后通过检查猪的各种组织/器官 使用敏感的分子技术来确定病毒持续存在的位置。 随后，申请者将移植长期感染EMCV的猪 组织转化为SCID(严重联合免疫缺陷)小鼠 人外周血淋巴细胞免疫抑制治疗 (HU-PBL-ISCID)，以确定此类组织传播的风险 疾病。HU-PBL-ISCID小鼠将作为免疫抑制模型 移植患者的系统。该培训计划还将要求 观察和协助猴子对猴子(异体)和猪对猴子的工作的候选人 (Xeno-)在现有的移植实验室进行移植。这个 长期目标是移植含有持久性物质的猪器官/组织 猪病毒进入灵长类动物，以确定患病的风险。

DESCRIPTION (Adapted from applicant's abstract) 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.