AN AFRICAN GREEN MONKEY MODEL OF DENGUE HEMORRHAGIC FEVER

登革出血热非洲绿猴模型

• 批准号: 8358010
• 负责人: Katharine Nina Bossart
• 金额: $ 5.4万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358010
• 关键词: Animal Model; Animals; Biological; Biological Assay; Cercopithecus aethiops; Cercopithecus pygerythrus; Cessation of life; Clinical; Coagulation Process; Data; Dengue; Dengue Hemorrhagic Fever; Dengue Virus; Development; Disease; Exanthema; Fever; Funding; Goals; Grant; Human; Immune; Individual; Infection; Mediating; Modeling; Monitor; National Center for Research Resources; New England; Pathway interactions; Pilot Projects; Predisposition; Primate Diseases; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Sampling; Source; Symptoms; Time; United States National Institutes of Health; Viral Load result; base; cost; drug development; nonhuman primate; therapeutic vaccine

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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 登革热病毒每年感染5000多万人，导致重大疾病和大约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人类所见的疾病，因此，疫苗和治疗药物的开发进展缓慢。在目前的项目中，我们将检查非洲绿猴(Cercopithecus Atheiops)对登革热病毒的易感性。该项目的目标是开发一种新的登革热病毒动物模型，这种模型与人类身上看到的疾病非常相似，包括登革出血热的发展。目前的研究是一项协作性的先导研究，只使用了少量的动物。 在这些研究中，我们将使用一种新的登革热病毒分离物，这种病毒起源于非人类灵长类动物，并在人类中引起登革热出血热。这种新的登革热分离株将用于感染非人类灵长类动物，感染后将对疾病进行21天的监测，包括外部临床症状、皮疹或不规则和发烧。将在不同的时间点收集生物样本，并将使用标准微生物学和临床分析来评估病毒载量、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，我们将能够确定长颈鹿是否是一个可行的宿主，以开发一种模仿人类疾病的严重登革热介导性疾病的新模型。