RISK OF PORCINE PICORNAVIRUS IN XENOTRANSPLATATION

描述 （摘自申请人摘要）这项研究职业奖旨在 为候选人提供异种移植生物学方面的研究经验 和猪传染病动物模型， 建立一个异种动物病的研究项目 这位候选人有 细胞和分子病毒学及小鼠动物研究经验 他是一名模特，最近在纽约大学担任教职。 明尼苏达州，这是著名的研究领域的移植和 猪的疾病 该研究项目将调查 持久性猪病毒，可能无法通过标准筛查检测到 在异种移植后在人类中变得致病的方法。 的 实验将利用猪脑心肌炎病毒（EMCV）， 已被证明会导致物种感染，以评估人类感染的风险 通过检查各种猪组织/器官 利用敏感的分子技术来确定病毒在哪里存在。 随后，申请人将移植慢性EMCV感染的猪 将组织植入用重组的SCID（严重联合免疫缺陷）小鼠中， 人外周血淋巴细胞随后免疫抑制处理 （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的模型。 移植患者的系统。 该培训计划还将要求 候选人观察和协助猴对猴（allo-）和猪对猴 在已建立的移植实验室中进行（异种）移植。 的 长期目标是移植猪器官/组织， 将猪病毒注入灵长类动物体内，以确定患病风险。

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.