Discovery and characterization of emerging, engineered and unrecognized pathogens

该项目的总体目标是确定导致人类疾病的新病原体， 一个灵活高效的系统，用于快速识别和分析新兴或工程化的 剂.这将服务于四个目的：（i）提高对疫情的准备，（ii）描述新病毒的特征 我们已经在急性病患者的标本中发现了这些病毒（迄今为止发现了7种新型病毒），（iii） 确定其他新的致病性病毒，以及（iv）提供对人类病毒组的新理解。到 为此，我们组建了一个国际合作小组，系统地解决病因学问题， 使用尖端的分子基因组方法， 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，这是共同负责 每年约有600万人死亡。最全面的分析未能确定和病因 脑炎70%，呼吸道感染30%，胃肠炎40%。此外该 新的感染因子的出现，其中许多表现出这些特征的临床症状， 疾病，强调迫切需要确定能够引起这些疾病的病毒的完整谱 疾病在该提案中，我们提出了一个用于识别新型病毒的集成管道， 这些病毒的特征，以及它们的生物学相关性的定义。为了识别新型病毒， 互补的基因组方法，泛病毒DNA微阵列和大规模测序，将应用于 以高度全面和最小偏差的方式分析临床标本。这些方法具有 在2003年SARS爆发期间，这种新型的WU病毒曾被用来鉴定SARS是一种新型冠状病毒， 多瘤病毒和多种新型病毒。我们将确定基因组 使用分子、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，将优先考虑与之相关的病毒，以供未来研究使用 旨在阐明病毒的基本生物学及其潜在致病性。

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.