Clinical and viral genomic approaches to evaluate the emergence of Powassan virus

项目摘要/摘要 新出现的病毒病原体对人类健康构成了持续的、不可预测的威胁。这份提案提出了 一个职业发展研究和培训计划，试图了解鲍瓦桑的出现 病毒，一种由壁虱传播的黄病毒，会导致严重的神经感染。鲍瓦桑病毒是由硬蜱传播的。 在新英格兰和其他莱姆病流行地区，人们越来越多地检测到肩部扁虱。然而， 关于波瓦桑病毒感染的频率，它引起的疾病范围，以及 导致人类感染的病毒株。候选人将使用病毒基因组方法来理解 鲍瓦桑病毒在硬蜱中的进化，并将表征其频率、临床表现和病毒 人类鲍瓦桑病毒的基因组学，这是迄今为止对这种病毒进行的最全面的研究。 为了提供理解人类感染日益增多的检测的背景，候选人将首先 调查新英格兰各地采集的扁虱中的鲍瓦桑病毒的分子流行病学。这个 候选人将直接从扁虱样本中对鲍瓦桑病毒基因组进行测序并进行系统进化 分析以评估是否存在病毒种群的增长，这可能有助于 人类感染。为了全面描述人类感染鲍瓦桑病毒的特征，候选人将 从存在这种感染风险的患者队列中筛选样本。这项研究将界定 鲍瓦桑病毒在神经系统和非神经系统感染中的感染频率，以及Will序列 从人类感染鲍瓦桑病毒基因组来指导致病机理的研究。总之，这项工作将 为了解波瓦桑病毒感染的出现和影响提供关键一步，目标是 为进一步努力预防和治疗提供指导。该提案与NIAID的优先事项一致 目的了解和预防硬蜱传播的感染。 K08指导临床科学家研究职业发展奖建议对候选人进行培训 在病毒学的实验室和计算技术方面。候选人的背景包括博士学位 病毒学研究培训和传染病临床专门化。在目前的提案中，她将 学习血清学、病毒基因组测序、生物信息学和系统发育学方面的新技能 培训和实际应用。马萨诸塞州综合医院宽阔的刺激环境 学院和哈佛大学非常适合拟议的培训计划，包括课程工作 在计算生物学，临床和研究研讨会，以及职业发展研讨会。候选人 将由一个由病毒基因组学和翻译学专家组成的导师咨询委员会指导 研究。通过这次研究和培训，她将处于非常有利的地位，可以开始她的职业生涯 研究对公共卫生具有重要意义的新病毒的独立内科科学家。

Project Summary / Abstract Emerging viral pathogens represent an ongoing, unpredictable threat to human health. This proposal presents a career development research and training program that seeks to understand the emergence of Powassan virus, a tick-borne flavivirus that causes severe neurological infection. Powassan virus is transmitted by Ixodes scapularis ticks and has been increasingly detected in New England and other Lyme-endemic areas. However, very little is known about the frequency of Powassan virus infection, the spectrum of illness it causes, and the viral strains that cause human infection. The candidate will use a viral genomic approach to understand the evolution of Powassan virus in ticks, and will characterize the frequency, clinical manifestations, and viral genomics of Powassan virus in humans, in the most comprehensive investigation of this virus to date. To provide context for understanding the increasing detection of human infections, the candidate will first investigate the molecular epidemiology of Powassan virus in ticks collected throughout New England. The candidate will sequence Powassan virus genomes directly from tick samples and perform phylogenetic analyses to assess whether there has been growth of the viral population that could contribute to increasing human infection. To comprehensively characterize Powassan virus infection in humans, the candidate will screen samples from established cohorts of patients who are at risk for this infection. This study will define the frequency of Powassan virus infection in both neurological and non-neurological infection, and will sequence Powassan virus genomes from human infection to guide studies of pathogenesis. Altogether, this work will provide a critical step in understanding the emergence and impact of Powassan virus infection, with the goal of guiding for further efforts towards prevention and treatment. The proposal aligns with the NIAID priority objective to understand and prevent tick-borne infections. This K08 Mentored Clinical Scientist Research Career Development Award proposes training for the candidate in both laboratory and computational techniques in virology. The candidate's background includes doctoral research training in virology and clinical specialization in Infectious Disease. In the current proposal, she will learn new skills in serology, viral genome sequencing, bioinformatics, and phylogenetics through both formal training and practical application. The stimulating environment of Massachusetts General Hospital, the Broad Institute, and Harvard University are extremely well suited to the proposed training plan, including coursework in computational biology, clinical and research seminars, and career development workshops. The candidate will be guided by a mentorship advisory committee comprised of experts in viral genomics and translational research. Through this research and training, she will become very well positioned to launch her career as an independent physician scientist studying emerging viruses of public health importance.