Discovery of Novel Human Pathogens

有效应对生物威胁与有效应对新出现的生物威胁密不可分 病原体[“打击生物恐怖主义：科学和技术的作用”，美国国家科学院2002年报告]。病因学 许多人类疾病都是未知的，但可能是传染性的。新病毒可以进入人类种群 具有毁灭性的影响，故意释放新的或经过改造的制剂是一种危险。何时是新的 技术被应用于检测新出现的病原体或与疾病相关的病原体 未知的病因，新的病原体被发现，导致人类健康的重大进步 以及开发新的有用的诊断学。这些诊断，特别是如果它们相对 在他们能检测到的东西上不偏不倚可以在检测新出现的病原体或生物威胁方面发挥作用。因此， 新毒剂的发现与对生物恐怖主义的有效反应齐头并进。鉴于这些， 考虑到，我们建议发展基础设施和专业知识，以确定新的人类代理人 项目中的疾病：(I)将最先进的技术引入发现新技术的问题 病原体，(Ii)将这些技术和方法以严肃和高通量的方式应用于临床 精心挑选的样本中含有未知或新出现的病原体，以及(Iii)通过这一努力带来新的 在线诊断和发现工具，用于识别临床标本中的流行病原体。潜力 该项目的成果包括与人类疾病有关的新病原体、基础设施和 需要训练有素的专业人员在疫情爆发期间识别病原体，并进行诊断测试和 技术。到目前为止，我们已经发现了一种新的人类病毒，并开发了 需要样品管道和技术。我们建议通过三个目标继续这一项目。目标2d是一个 以新技术的开发和验证为基础的新目标。 目的1)寻找适合病原菌发现实验的临床材料。 目的2)通过应用以下方法鉴定新病原体： 目的2a)泛病毒微阵列技术。 目标2)代表性差异分析(RDA)。 目的2c)免疫功能严重受损的小鼠对药物的转运。 目的2)大规模测序和信息学和信息学管道。 目的3)确定临床标本中是否存在新的病原体。

Effective responses to biological threats are inextricably related to effective responses to emerging pathogens [Countering Bioterrorism: the Role of Science and Technology, NAS report 2002]. The etiologies of many human diseases are unknown, but may be infectious. New viruses can enter the human population with devastating effect, and the intentional release of new or engineered agents is a danger. When new technologies are applied to the problem of detecting emerging agents or agents associated with diseases of unknown etiology, new pathogens have been discovered, resulting in significant advances in human health and in the development of new and useful diagnostics. These diagnostics, particularly if they are relatively unbiased in what they can detect can play a role in detecting emerging pathogens or biological threats. Thus, discovery of new agents walks hand in hand with effective responses to bioterrorism. In light of these considerations, we proposed to develop the infrastructure and expertise to identify new agents of human disease in a Project designed to: (i) bring the most advanced technologies to the problem of discovering new pathogens, (ii) apply these technologies and approaches in a serious and high throughput way to clinical samples carefully selected to contain unknown or emerging pathogens, and (iii) through this effort bring new diagnostic and discovery tools on line for identifying epidemic agents in clinical specimens. Potential deliverables from this Project include new pathogens associated with human disease, the infrastructure and trained professionals required to identify pathogens during an outbreak, and diagnostic tests and technologies. To date, we have delivered the discovery of one new human virus, and have developed the needed sample pipeline and technologies. We propose to continue this project via three Aims. Aim 2d is a new Aim based on development and validation of new technologies. Aim 1) Identify clinical materials appropriate for pathogen discovery experiments. Aim 2) Identify novel pathogens by applying: Aim 2a) Pan-viral microarray technology. Aim 2b) Representational Difference Analysis (RDA). Aim 2c) Passage of agents in severely immunocompromised mice. Aim 2d) Mass sequencing and informatic and an informtics pipeline. Aim 3) Determine if novel pathogens are present in clinical samples.