Emerging Neuroviruses and Neurological Inflammatory Diseases

项目总结 最近在拉丁美洲和加勒比爆发的寨卡病毒和基孔肯雅热等虫媒病毒感染 各国已经发现了紧急病毒感染在神经炎性疾病发病率增加中的作用 脑炎、脊髓炎和格林-巴利综合征(GBS)等疾病。在这里，我们提出了一个多中心 哥伦比亚大学-医院地点模型，以促进临床、流行病学和病毒学监测 以及与新出现的感染相关的神经疾病的研究。已经建立的模式是 美洲出现的神经病毒研究(NEAS)将作为神经疾病的观察站 与新出现的病毒感染有关，并将促进建立和加强 哥伦比亚应对新出现的病毒疾病及其威胁的可持续研究能力 神经系统并发症。根据我们帮助确定临床特征的初步研究， 哥伦比亚寨卡病毒相关GBS的免疫学和病毒学特征(Parra等人，《新英格兰医学杂志》2016) 假设受紧急病毒影响地区成人人群中的急性神经问题 感染是由先前建立的循环虫媒病毒驱动的复杂宿主-病毒相互作用造成的 (如登革热、肠道病毒)以及新出现的病原体(如寨卡病毒和基孔肯雅热)； 病毒基因型以及宿主对先前病毒感染的免疫反应驱动致病性和 神经系统疾病的严重程度。为了解决这一假设，这项提议的具体目标是：1)利用 建立可持续评估急性神经炎性疾病的NEAS模型 例如GBS和脑炎-脊髓炎，并确定紧急感染在疾病发展中的作用 这类并发症，2)实施最先进的技术，提高对新兴疾病的诊断 病原体在急性神经炎症性疾病发病中的作用；以及3)建立一个培训计划，以 提高哥伦比亚研究人员在使用下一代分子和免疫学方面的能力 元基因组学和病原体发现研究中的技术和计算生物学方法。我们 将利用过去和现在在招募患者和收集生物样本方面的经验 Neas队列研究人群，使用最先进的免疫学分析，下一代测序， 和大规模多重病毒多肽分析(VirScan)来实现这一目标。我们相信这一发现 该项目将对公共卫生产生重大影响，并将解决与病毒多样性和 对疾病严重性的影响、了解疾病发病机制、管理和 疫苗研发。该项目还将通过投资于以下项目促进哥伦比亚的能力建设 临床和翻译研究，以更好地描述新出现的病毒疾病的神经系统并发症。

PROJECT SUMMARY The recent outbreaks of arboviral infections such as Zika and Chikungunya in Latin American and Caribbean countries have uncovered the role of emergent viral infections in the increased incidence of neuroinflammatory disorders such as encephalitis, myelitis and Guillain-Barré syndrome (GBS). Here, we propose a multi-center model of university-hospital sites in Colombia to facilitate clinical, epidemiological, and virological surveillance and research of neurological disorders associated with emerging infections. The model already established as the Neurovirus Emerging in the Americas Study (NEAS), will serve as an observatory of neurological disorders associated with emerging viral infections and will facilitate the long-term goals of building and strengthening sustainable research capacity in Colombia to address the emerging threat of viral illnesses and their neurological complications. Based on our preliminary studies that helped to characterize clinical, immunological and virological features of Zika-associated GBS in Colombia (Parra et al., NEJM 2016), we hypothesize that acute neurological problems in the adult population of areas affected by emergent viral infections result from complex host-viral interactions driven by previously established circulating arboviruses (e.g., dengue, enteroviruses) as well as emergent pathogens (e.g., Zika and Chikungunya); and that variations in viral genotype as well as host immunological responses to previous viral infections drive pathogenicity and severity of neurological disease. To address this hypothesis, the specific aims of this proposal are: 1) To utilize the NEAS model to establish a sustainable approach for assessment of acute neuroinflammatory disorders such as GBS and encephalitis-myelitis and determine the role of emergent infections in the development of such complications, 2) To implement state of the art technologies to improve the diagnosis of emerging pathogens in the onset of acute neuroinflammatory disorders; and 3) To establish a training program to enhance the competence of Colombian researchers in the use of next generation molecular and immunological techniques, and computational biological approaches in metagenomics and pathogen discovery studies. We will take advantage of the past and present experience with patient recruitment and biosample collection in the NEAS cohort study population, the use of state-of-the-art immunological assays, next generation sequencing, and massive multiplexed viral peptides assay (VirScan) to achieve such aims. We believe the findings of this project will have a major public health impact and will address important questions related to viral diversity and impact on disease severity, information needed for understanding disease pathogenesis, management and vaccine development. This project will also contribute to building up capacity in Colombia by investing in clinical and translational research to better characterize neurological complications of emerging viral diseases.