DETERMINATION OF AGE-RELATED DEFECTS IN CHIKUNGUNYA VIRUS INFECTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的目的是利用非人灵长类动物(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是一种NIAID C类生物制剂，是一种重新出现的虫媒病毒，最近在印度洋造成了大规模疫情。迄今为止，感染仅限于非洲和印度洋地区；然而，最近在欧洲爆发的疫情提高了全世界对这种使人衰弱和可能致命的病毒感染的认识。重要的是，现在在美国东南部的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被认为不会危及生命，但2005-2006年在印度洋的法国留尼汪岛上，有200多人与这种疾病有关。此外，病毒引起的关节炎可能会使人极度虚弱，在老年人中会持续数周至数年。涉及中枢神经系统感染的严重病例也被描述为免疫功能受损的人，包括老年人。我们建议比较CHIKV感染的病理生理学，并使用CHIKV感染的NHP模型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性增加的基础。到目前为止，我们已经进行了一项初步研究，以确定感染成年恒河猴所需的病毒株和剂量。我们已经确定了这些动物的免疫反应和病毒载量。接下来我们将感染年迈的恒河猴。

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.