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

评估波瓦桑病毒出现的临床和病毒基因组方法

基本信息

批准号：
10322092
负责人：
Anne L Piantadosi
金额：
$ 16.96万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-16 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10322092
关键词：
Acute Address Advisory Committees Area Babesia microti Bioinformatics Black-legged Tick Blood Screening Blood specimen Brain Case Series Cerebrospinal Fluid Characteristics Clinical Clinical Research Collection Communicable Diseases Computational Biology Computational Technique Computing Methodologies Detection Educational workshop Encephalitis Environment Evolution Foundations Freezing Frequencies Funding Future General Hospitals Genetic Variation Genomic approach Goals Growth Health Human Immunoglobulin M Incidence Infection Institutes Investigation Ixodes K-Series Research Career Programs Laboratories Learning Length Lyme Disease Massachusetts Measures Mentors Mentorship Methodology Methods Middle East Respiratory Syndrome Coronavirus Molecular Epidemiology National Institute of Allergy and Infectious Disease Neurologic New England Pathogenesis Patients Persons Phylogenetic Analysis Physicians Population Population Growth Positioning Attribute Powassan virus Prevention Prospective Studies Public Health Publishing Quantitative Reverse Transcriptase PCR Reporting Research Research Training Sampling Scientist Serology Structure Techniques Tick-Borne Infections Ticks Training Training Programs Translational Research Universities Viral Viral Genome Viremia Virus Virus Diseases Work ZIKA base career career development clinical diagnosis cohort emerging pathogen genome sequencing infection risk metagenomic sequencing novel virus pathogen pathogenic virus practical application prevent research clinical testing response skills tick transmission tick-borne flavivirus tick-borne pathogen vector viral RNA viral genomics virology

项目摘要

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.

项目概要/摘要新出现的病毒病原体对人类健康构成持续的、不可预测的威胁。该提案提出职业发展研究和培训计划，旨在了解 Powassan 的出现病毒，一种蜱传黄病毒，可引起严重的神经感染。波瓦桑病毒通过硬蜱传播肩胛蜱蜱在新英格兰和其他莱姆病流行地区越来越多地被发现。然而，人们对波瓦桑病毒感染的频率、其引起的疾病谱以及其影响知之甚少。引起人类感染的病毒株。候选人将使用病毒基因组方法来了解 Powassan 病毒在蜱中的进化，并将表征其频率、临床表现和病毒人类波瓦桑病毒的基因组学，这是迄今为止对该病毒最全面的研究。为了提供了解不断增加的人类感染检测的背景，候选人将首先研究在新英格兰各地收集的蜱虫中波瓦桑病毒的分子流行病学。这候选人将直接从蜱样本中对 Powassan 病毒基因组进行测序并进行系统发育进行分析以评估病毒种群的增长是否可能导致病毒数量增加人类感染。为了全面描述人类波瓦桑病毒感染的特征，候选人将从已确定的有感染风险的患者群体中筛查样本。这项研究将定义波瓦桑病毒感染在神经系统和非神经系统感染中的频率，并将排序人类感染的波瓦桑病毒基因组可指导发病机制研究。总而言之，这项工作将为了解波瓦桑病毒感染的出现和影响提供了关键的一步，目标是为进一步做好预防和治疗工作提供指导。该提案符合 NIAID 的优先事项目的是了解和预防蜱传感染。 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病毒学的实验室和计算技术。候选人背景包括博士病毒学和传染病临床专业研究培训。在目前的提案中，她将通过正式课程学习血清学、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。麻省总医院 (Massachusetts General Hospital) 的刺激环境研究所和哈佛大学非常适合拟议的培训计划，包括课程作业计算生物学、临床和研究研讨会以及职业发展研讨会。候选人将受到由病毒基因组学和转化专家组成的指导咨询委员会的指导研究。通过这项研究和培训，她将非常有能力开启自己的职业生涯研究对公共卫生具有重要意义的新兴病毒的独立医师科学家。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Phylodynamics of deer tick virus in North America.

DOI：
10.1093/ve/vead008
发表时间：
2023
期刊：
Virus evolution
影响因子：
5.3
作者：
通讯作者：

Enhanced Virus Detection and Metagenomic Sequencing in Patients with Meningitis and Encephalitis.

DOI：
10.1128/mbio.01143-21
发表时间：
2021-08-31
期刊：
mBio
影响因子：
6.4
作者：
Piantadosi A;Mukerji SS;Ye S;Leone MJ;Freimark LM;Park D;Adams G;Lemieux J;Kanjilal S;Solomon IH;Ahmed AA;Goldstein R;Ganesh V;Ostrem B;Cummins KC;Thon JM;Kinsella CM;Rosenberg E;Frosch MP;Goldberg MB;Cho TA;Sabeti P
通讯作者：
Sabeti P

Unrecognized introductions of SARS-CoV-2 into the US state of Georgia shaped the early epidemic.

DOI：
10.1093/ve/veac011
发表时间：
2022
期刊：
Virus evolution
影响因子：
5.3
作者：
Babiker A;Martin MA;Marvil C;Bellman S;Petit Iii RA;Bradley HL;Stittleburg VD;Ingersoll J;Kraft CS;Li Y;Zhang J;Paden CR;Read TD;Waggoner JJ;Koelle K;Piantadosi A
通讯作者：
Piantadosi A

Powassan Virus Encephalitis.