Exploiting Viral Genomics to Understand Disease

研究项目1的重点是来自人类的重要地方性病毒病原体和来自动物的病毒 具有很强的人畜共患病潜力的宿主。高通量下一代全基因组测序 (NGS)，结合生物信息学算法，将被用于对来自 代表7种病毒物种的10,000多个菌株。这将表征一年来的遗传多样性 一系列病毒家族，包括许多NIAID优先病原体，以了解关键的进化 病毒进化、致病机制、传播和/或抗病毒耐药性的核心机制。具体来说，我们 目的：1)比较和对比体内传播的病毒的遗传多样性和进化动态 和/或人类和动物宿主之间的关系，2)阐明病毒-宿主-微生物组决定因素 影响病毒致病机制，以及3)进行深度测序以了解宿主内病毒的多样性， 传播动力学和抗病毒抵抗力。 总的来说，该项目将使用多种基因组学方法(例如基因组测序、元基因组学、 和转录学)为科学界提供广泛使用的基因组数据集，从重要的 病毒式家庭。这些数据将使用系统发育学和其他生物信息学算法进行分析，以显示 这些病原体的时空演变。最后，生成的数据将识别、跟踪和 预测抗原漂移/转移、重组、逃避自然或疫苗诱导的宿主免疫反应， 抗病毒耐药性、种间和种内传播以及宿主的共生反应 微生物区系对病毒感染的影响。从这些研究中产生的信息将帮助我们产生更好的 疫苗和抗病毒药物，以及数据集将被证明对快速应对新出现的 自然或由于生物恐怖主义而产生的病原体(即大流行防备)。

Research' Project 1 focuses on significant endemic viral pathogens from humans and viruses from animal hosts that have strong zoonotic potential. High-throughput whole-genome next-generation sequencing (NGS), combined with bioinformatics algorithms, will be used to sequence and analyze the genomes from more than 10,000 strains representing seven viral species. This will characterize the genetic diversity over a range of virus families, including many NIAID priority pathogens, to understand critical evolutionary mechanisms central to viral evolution, pathogenesis, transmission, and/or antiviral resistance. Specifically we aim to: 1) compare and contrast the genetic diversity and evolutionary dynamics of viruses circulating within and/or between humans and animal reservoirs, 2) elucidate viral-host-microbiome determinants that influence viral pathogenesis, and 3) perform deep sequencing to understand intra-host viral diversity, transmission dynamics, and antiviral resistance. Collectively, this project will use multiple genomics approaches (e.g., genomic sequencing, metagenomics, and transcriptomics) to provide the scientific community with genomic data sets of broad use from important viral families. These data will be analyzed using phylogenetics and other bioinformatics algorithms to show the spatial and temporal evolution of these pathogens. Finally, the data generated will identify, track, and predict antigenic drift/shift, recombination, escape from natural or vaccine-induced host immune responses, antiviral resistance, inter- and intra-species transmission, and the response of a host's commensal microbiota to viral infection. The information generated from these studies will help us to produce superior vaccines and antivirals, and the data sets will prove critical for rapid responses to the emergence of novel pathogens (i.e., pandemic preparedness) that arise naturally or as a result of bioterrorism.