Bioinformatics for Biodefense: Comparison of Global Transcriptional Host Responses across Non-Human Primates Infected with Anthrax, Poxviruses, and Filoviruses

The World Health Organization recognizes Anthrax, Monkeypox, Smallpox, Ebola, and Marburg as high-risk infectious agents. In addition, the United States Centers for Disease Control has characterized four out of five of these agents as Category A bio-threats. These pathogens are characterized by mortality rates that range between ten and ninety percent. Furthermore, while all of these pathogens are known to trigger an unbalanced immune response in the host, there has been no analysis comparing how the global peripheral immune response varies with each type of infection. To address this question, we examined the host responses infected non-human primates. Utilizing custom microarray technology, we investigated the regulation of 18,000 genes through relative host mRNA levels throughout the course of each infection. A computational pipeline was developed to process each sample, comparing post-infection gene expression levels to a their pre-infection baseline. Genes whose expression varied significantly from baseline were selected for functional enrichment and pathway analysis. Comparing these results allowed us to elucidate commonalities and differences between the five infection mechanisms. For instance, our analysis confirms the modulation of particular immune response pathways. Specifically, we were able to identify the interferon responsive STAT1 gene and the Toll-Like Receptor Pathway as prime conserved components that are altered in across all infections. This work represents a comparative genomic expression analysis of the temporal pathogen-host responses in the context of five separate in vivo primate infection studies. Our results will guide future experiments that provide insight into disease pathogenesis and potential therapeutic targets.