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

• 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
• 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

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.

项目总结/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。该提案提出 职业发展研究和培训计划，旨在了解波瓦桑的出现 病毒，蜱传黄病毒，导致严重的神经系统感染。Powassan病毒由硬蜱传播 肩胛蜱，并已越来越多地发现在新英格兰和其他莱姆流行地区。然而，在这方面， 关于Powassan病毒感染的频率，它引起的疾病谱以及 导致人类感染的病毒株。候选人将使用病毒基因组方法来了解 蜱中Powassan病毒的进化，并将描述频率，临床表现和病毒 人类中的Powassan病毒基因组学，迄今为止对该病毒进行了最全面的调查。 为了提供理解人类感染检测增加的背景，候选人将首先 调查在整个新英格兰收集的蜱中的Powassan病毒的分子流行病学。的 候选人将直接从蜱样本中测序Powassan病毒基因组，并进行系统发育分析。 分析，以评估是否有病毒种群的增长，可能有助于增加 人类感染为了全面表征人类中的Powassan病毒感染，候选人将 从已确定的有感染风险的患者队列中筛选样本。本研究将定义 Powassan病毒感染在神经系统和非神经系统感染中的频率，并将序列 从人类感染的波瓦桑病毒基因组指导发病机制的研究。总之，这项工作将 为了解Powassan病毒感染的出现和影响提供了关键一步，其目标是 指导进一步努力预防和治疗。该提案符合NIAID的优先事项 目的了解蜱媒感染情况，预防蜱媒感染。 K 08指导临床科学家研究职业发展奖为候选人提供培训 在病毒学的实验室和计算技术中。候选人的背景包括博士 病毒学研究培训和传染病临床专业化。在目前的提案中，她将 学习血清学，病毒基因组测序，生物信息学和遗传学的新技能，通过两个正式的 培训和实际应用。马萨诸塞州总医院的激励环境， 研究所和哈佛大学非常适合拟议的培训计划，包括课程 在计算生物学，临床和研究研讨会，和职业发展讲习班。候选 将由一个由病毒基因组学和翻译专家组成的导师咨询委员会指导。 research.通过这项研究和培训，她将成为非常好的定位，启动她的职业生涯， 研究新出现的对公共卫生有重要意义的病毒的独立医生科学家。

项目成果

Powassan Virus Encephalitis.

• DOI: 10.1016/j.idc.2022.03.003
• 发表时间: 2022-09
• 期刊: INFECTIOUS DISEASE CLINICS OF NORTH AMERICA
• 影响因子: 4.4
• 作者: Piantadosi, Anne;Solomon, Isaac H.
• 通讯作者: Solomon, Isaac H.

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

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