DETERMINATION OF AGE-RELATED DEFECTS IN CHIKUNGUNYA VIRUS INFECTION

基孔肯雅病毒感染中年龄相关缺陷的测定

• 批准号: 8173293
• 负责人: DANIEL N STREBLOW
• 金额: $ 4.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173293
• 关键词: Adult; Africa; Animals; Arboviruses; Arthritis; Awareness; Biological Products; Categories; Central Nervous System Infections; Chikungunya virus; Computer Retrieval of Information on Scientific Projects Database; Culicidae; Defect; Disease; Disease Outbreaks; Elderly; Europe; Functional disorder; Funding; Goals; Grant; Immune; Immune response; Indian Ocean; Individual; Infection; Institution; Life; Macaca mulatta; Modeling; National Institute of Allergy and Infectious Disease; Predisposition; Research; Research Personnel; Resources; Reunion Island; Severity of illness; Source; Southeastern United States; United States National Institutes of Health; Viral Load result; Virus; Virus Diseases; adaptive immunity; age related; aged; base; dosage; nonhuman primate

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this study is to elucidate the immunological basis of increased susceptibility of aged individuals to Chikungunya virus (CHIKV) infection using a non-human primate (NHP) model. CHIKV, a NIAID Category C Biological Agent, is a re-emerging arbovirus that caused massive recent outbreaks in the Indian Ocean. To date, infections have been limited to Africa and the Indian Ocean Region; however, recent outbreaks in Europe have increased worldwide awareness of this debilitating and potentially lethal viral infection. Importantly, the mosquitoes that transmit CHIKV are now found in much of the Southeastern United States making CHIKV spread possible in the US. While CHIK is not considered to be life threatening, over 200 fatalities were associated with the disease on the French island of Reunion in the Indian Ocean in 2005-6. Additionally, virus-induced arthritis can be extremely debilitating and last for weeks to years in the aged. Severe cases involving infections of the central nervous system have also been described in immune compromised individuals including the elderly. We propose to compare the pathophysiology of CHIKV infection and identify age-related differences in adaptive immunity that underlie increased disease severity in the elderly using a NHP model of CHIKV infection. To date we have performed an initial study to identify the virus strain and dosage that are required for infection of adult Rhesus macaques. We have characterized the immune response and viral load in these animals. We will next infect aged Rhesus macaques.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 本研究的目的是利用非人类灵长类动物 (NHP) 模型阐明老年人对基孔肯雅病毒 (CHIKV) 感染易感性增加的免疫学基础。 CHIKV 是 NIAID C 类生物制剂，是一种重新出现的虫媒病毒，最近在印度洋引起了大规模爆发。迄今为止，感染仅限于非洲和印度洋地区；然而，欧洲最近爆发的疫情提高了全世界对这种使人衰弱且可能致命的病毒感染的认识。重要的是，目前美国东南部大部分地区都发现了传播 CHIKV 的蚊子，这使得 CHIKV 在美国传播成为可能。虽然 CHIK 不被认为会危及生命，但 2005 年 6 月，印度洋法属留尼汪岛有 200 多人死于该病。此外，病毒引起的关节炎可能会使老年人极度虚弱，并持续数周至数年。在包括老年人在内的免疫功能低下的个体中也有涉及中枢神经系统感染的严重病例的报道。我们建议使用 CHIKV 感染的 NHP 模型来比较 CHIKV 感染的病理生理学，并确定与年龄相关的适应性免疫差异，这些差异是老年人疾病严重程度增加的基础。迄今为止，我们已经进行了初步研究，以确定感染成年恒河猴所需的病毒株和剂量。我们已经表征了这些动物的免疫反应和病毒载量。接下来我们将感染老年恒河猴。