Discovery of Novel Human Pathogens

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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.