Emerging Neuroviruses and Neurological Inflammatory Diseases

项目摘要 最近在拉丁美洲和加勒比地区爆发的寨卡和基孔肯雅等虫媒病毒感染 许多国家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， 疾病如脑炎、肌萎缩和格林-巴利综合征（GBS）。在这里，我们提出了一个多中心 哥伦比亚大学-医院选址模式，以促进临床、流行病学和病毒学监测 以及与新发感染相关的神经系统疾病的研究。该模型已经建立， 美洲研究中出现的神经病毒（NEAS）将作为神经系统疾病的观察站 与新出现的病毒感染有关，并将促进建立和加强 哥伦比亚的可持续研究能力，以应对病毒性疾病及其 神经系统并发症根据我们的初步研究，有助于描述临床， 哥伦比亚Zika相关GBS的免疫学和病毒学特征（Parra等，NEJM 2016），我们 假设急性病毒感染地区成年人群中急性神经系统问题 感染是由先前建立的循环虫媒病毒驱动的复杂宿主-病毒相互作用引起的 (e.g.,登革热，肠道病毒）以及新出现的病原体（例如，寨卡病毒和基孔肯雅病毒）; 在病毒基因型以及宿主对先前病毒感染免疫应答中， 神经系统疾病的严重程度。为了解决这一假设，本提案的具体目标是：1）利用 NEAS模型建立急性神经炎性疾病评估的可持续方法 如GBS和脑炎-脑炎，并确定紧急感染在发展中的作用， 2）实施最先进的技术，以改善对新兴并发症的诊断， 病原体在急性神经炎性疾病的发病;和3）建立一个培训计划， 提高哥伦比亚研究人员使用下一代分子和免疫学技术的能力， 技术，以及宏基因组学和病原体发现研究中的计算生物学方法。我们 将利用过去和现在在患者招募和生物样本采集方面的经验， NEAS队列研究人群，使用最先进的免疫学检测，下一代测序， 和大规模多重病毒肽测定（VirScan）来实现这些目的。我们认为， 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有关的重要问题， 对疾病严重程度的影响，了解疾病发病机理所需的信息， 疫苗研发。该项目还将通过投资于以下方面，促进哥伦比亚的能力建设： 临床和转化研究，以更好地表征新兴病毒性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.