Discovery and characterization of emerging, engineered and unrecognized pathogens

该项目的总体目标是识别导致人类疾病的新病原体，并建立 灵活而高效的系统，用于快速识别和分析新兴或工程 探员们。这将有四个目的：(一)改进对暴发的准备，(二)确定新病毒的特征 我们已经在急病患者的样本中发现了这种病毒(到目前为止发现了7种新病毒)，(Iii) 确定其他新的致病病毒，以及(Iv)提供对人类病毒体的新理解。至 为此，我们组建了一个国际合作团队，系统地解决病因问题 使用尖端的分子基因组方法结合 经典的免疫学、病毒学和流行病学方法。在这个项目中，我们将主要关注三个方面 疾病、脑炎、呼吸道感染和胃肠炎，这些疾病共同导致 每年约有600万人死亡。最全面的分析无法识别和确定病因 该药在70%的脑炎，-30%的呼吸道感染和-40%的胃肠炎。此外， 出现新的感染性病原体，其中许多表现出这些疾病的临床症状 疾病，强调了确定能够导致这些疾病的完整病毒谱的迫切需要 疾病。在这项建议中，我们提出了一种用于鉴定新病毒的集成管道， 这些病毒的特征，以及它们的生物学相关性的定义。为了识别新的病毒，有两种 互补的基因组方法学、泛病毒DNA微阵列和大规模测序将被应用于 以高度全面和最小偏见的方式分析临床标本。这些方法有 曾在2003年疫情期间被用来确定SARS是一种新的冠状病毒，小说吴 腹泻患者粪便中的多瘤病毒和多种新病毒。我们将确定基因组 用分子、流行病学和生物学方法研究新型病毒的结构和生物学相关性 血清流行病学标准。然后，将对看似相关的病毒进行优先排序，以供未来研究 旨在阐明病毒的基本生物学以及它们的潜在致病性。

The overall goals of this project are to identify novel pathogens responsible for human disease and to create a flexible and highly effective system for the rapid identification and analysis of emerging or engineered agents. This will serve four purposes: (i) improve preparedness for outbreaks, (ii) characterize new viruses that we have already discovered in specimens from acutely ill patients (7 novel viruses identified to date), (iii) identify additional new pathogenic viruses, and (iv) provide new understanding of the human virome. To these ends, we have assembled an international collaborative team to systematically address the etiologies of a number of acute human illnesses using cutting edge molecular genomic approaches combined with classical immunological, virologic and epidemiologic methods. In this project, we will focus primarily on three diseases, encephalitis, respiratory tract infection, and gastroenteritis, which are collectively responsible for approximately 6,000,000 deaths annually. The most comprehensive analyses fail to identify and etiologic agent in 70% of encephalitis, -30% of respiratory tract infection and -40% of gastroenteritis. In addition, the emergence of new infectious agents, many of which manifest the clinical symptoms characteristic of these diseases, accentuates the critical need to define the complete spectrum of viruses capable of causing these diseases. In this proposal we present an integrated pipeline for identification of novel viruses, characterization of these viruses, and definition of their biological relevance. To identify novel viruses, two complementary genomic methodologies, pan-viral DNA microarrays and mass sequencing, will be applied to analyze clinical specimens in a highly comprehensive and minimally biased fashion. These methods have been previously used to identify SARS as a novel coronavirus during the 2003 outbreak, the novel WU polyomavirus and multiple novel viruses in stool from diarrhea patients. We will determine the genomic structure and biological relevance of novel viruses using molecular, epidemiological, and seroepidemiological criteria. Viruses that appear to be relevant will then be prioritized for future studies aimed at elucidating both the basic biology of the viruses as well as their potential pathogenicity.