Development of a Nonhuman Primate Model of Polyomavirus Disease

 描述(申请人提供)：人类多瘤病毒在越来越多的免疫受损患者中是越来越重要的机会性病原体，包括接受实体器官移植的患者和接受免疫抑制治疗的癌症、自身免疫和神经系统疾病的患者。缺乏多瘤病毒病的动物模型限制了我们研究多瘤病毒的免疫控制机制以及开发预防和治疗策略以减少多瘤病毒病的长期后遗症的能力。这个为期36个月的项目将建立在首席研究员和NIH资助的松鼠猴子育种和研究资源(SMBRR)建立的合作伙伴关系的基础上，以：1)确定松鼠猴子多瘤病毒(SMPyV)在易患人类多瘤病毒疾病的免疫抑制条件下重新激活的特征；2)探索人类多瘤病毒感染松鼠猴子并导致疾病的能力；以及3)测试现有抗病毒药物改善多瘤病毒重新激活的能力。拟议的研究将扩大SMBRR的研究范围，包括用于生物医学研究的与松鼠猴子健康相关的分子病毒学和免疫学技术。此外，这些研究将提供一个模型系统，可供其他研究人员用来研究多瘤病毒疾病的发病机制。

 DESCRIPTION (provided by applicant): The human polyomaviruses are increasingly important opportunistic pathogens among the growing population of immune compromised patients, including those with solid organ transplants and patients receiving immune suppressive treatments for cancer, autoimmune and neurologic diseases. The lack of an animal model of polyomavirus disease has limited our ability to study the mechanisms of immunologic control of polyomaviruses and to develop preventative and therapeutic strategies that could reduce the long-term sequelae of polyomavirus diseases. This 36-month project will build on the established partnership of the Principal Investigator and the NIH-funded Squirrel Monkey Breeding and Research Resource (SMBRR) to: 1) characterize the reactivation of the squirrel monkey polyomavirus (SMPyV) under conditions of immune suppression that predispose to human polyomavirus disease; 2) explore the ability of human polyomaviruses to infect and cause disease in squirrel monkeys; and, 3) test the ability of available antiviral agents to ameliorate polyomavirus reactivation. The proposed studies will broaden the scope of research at the SMBRR to include molecular virologic and immunologic techniques relevant to the health of squirrel monkeys used for biomedical research. In addition, these studies will deliver a model system that can be utilized by other researchers to study the pathogenesis of polyomavirus diseases.