AN AFRICAN GREEN MONKEY MODEL OF DENGUE HEMORRHAGIC FEVER

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 登革热病毒每年感染超过5000万人，造成重大疾病和大约50，000人死亡。目前，还没有登革热和登革出血热的动物模型来模拟在人类中观察到的疾病，因此，疫苗和治疗药物的开发进展缓慢。在目前的项目中，我们将研究非洲绿色猴（Cercopithecus aethiops）对登革病毒的易感性。该项目的目标是开发一种新的登革病毒动物模型，该模型与人类中发现的疾病密切相似，包括登革出血热的发展。目前的研究是一项合作试点研究，仅使用少量动物。 在这些研究中，我们将使用一种新的登革病毒分离株，该病毒起源于非人灵长类动物，并在人类中引起登革出血热。 这种新的登革热分离株将用于感染非人灵长类动物，并在感染后监测疾病21天，包括外部临床症状，皮疹或不规则和发烧。 将在不同时间点采集生物样本，并使用标准微生物和临床试验评价病毒载量、免疫参数和凝血途径。 通过分析所有的疾病症状和临床/微生物学数据，我们将能够确定Cercopithecus aethiops是否是一个可行的宿主，以开发一种模拟人类疾病的严重登革热介导疾病的新模型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Dengue virus infects over 50 million individuals each year causing significant disease and approximately 50,000 deaths. Currently, there are no animal models for Dengue fever and Dengue hemorrhagic fever which mimic the disease seen in humans and consequently, vaccine and therapeutic drug development have progressed slowly. In the current project we will examine the susceptibility of African green monkeys (Cercopithecus aethiops) to Dengue virus. The goal of this project is to develop a new animal model of Dengue virus that closely parallels the disease seen in humans, including the development of Dengue hemorrhagic fever. The current study is a collaborative pilot study that uses only a small number of animals. For these studies we will use a new isolate of dengue virus that originated in nonhuman primates and caused dengue hemorrhagic fever in a human. This new dengue isolate will be used to infect nonhuman primates and disease will be monitored for 21 days following infection, including outward clinical symptoms, skin rashes or irregularities and fever. Biological samples will be collected at various time points and viral loads, immune parameters and coagulation pathways will be evaluated using standard microbiological and clinical assays. By analyzing all of the disease symptoms and clinical/microbiological data, we will be able to determine if Cercopithecus aethiops are a viable host to develop a new model of severe dengue-mediated disease that mimics the disease seen in humans.