Host Gene Expression Responses to Biothreat and Infectious Agents: Implications for Mathematical Modeling of in vitro Responses
WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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Detection of exposure to biological threat agents currently uses culture methods, immunoassay and gene amplification and these methods constantly are being perfected for greater sensitivity. However, recent events have demonstrated that assessing exposure to a biological threat agent well in advance of onset of illness or at various stages post-exposure would be an important capability to have among the diagnostic options. There is an urgent need for better diagnostic tools that will be sensitive, rapid and unambiguous to identify pathogen exposures and aid in triage of affected personnel. Rationale Patterns of host cell transcription offers the potential for diagnosis of exposureinfection at a very early stage, even as early as 1 hour post-exposure. The ability of diagnostic assays to identify infected individuals during the prodromal period is essential for successful treatment or intervention following exposure and infection with many disease-causing agents. The identification of early markers of infection offers great promise for revolutionizing disease diagnosis. We have used gene microarray technology to characterized host gene expression responses rather than direct pathogen exposure to 14 biothreat and infectious agents using ex vivo exposures to each pathogen in peripheral blood mononuclear cells PBMC. We found sets of genes that readily identify the pathogen used. By a thorough evaluation of healthy human baseline gene expression using 75 diverse individuals, we identified genes with unambiguous responses for pathogen exposures. For 3 of these pathogenic agents, we have also carried out in vivo exposures in non-human primate models. Gene responses determined from blood drawn at various time periods post-exposure show clearly recognizable patterns of gene expression at remarkably early time frames.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research