This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The filovirus Marburg is a persistent and looming biothreat agent for several outbreak scenarios. Their high fatality rate and capacity for person to person transmission, combined with a lack of vaccines, therapeutics and diagnostics, are cause for concern in natural outbreaks, importation and bioterrorism. The re-emergences of Marburg in Angola (latest WHO report) continues to remind us of the disease potential in regions of Africa. Since the filoviral host reservoir(s) still remain(s) unidentified, outbreak prediction and control are very difficult. Since aerosolized virus is infectious and only a few virions are required for infectivity, filoviruses are regarded as potential bioweapons. Since some of the stockpiles and the scientists who created them remain unaccounted for, Marburg virus represents one of the most serious biothreats today. Consequently, there is an urgent need for us to rationalize the biothreat potentials. The observation that certain outbreaks of Marburg hemorrhagic fever result in varying degrees of mortality suggests that more virulent strains may alter the host response to infection. The host response is highly complex and involves a large number of cell types. We hypothesize that the differences in host transcriptome and proteome responses within these cell types can be used to characterize infection and identify Marburg variants with altered pathogenicity. These profiles will provide a deeper understanding of the meaning of biothreat potential at several molecular levels within the host response program. Furthermore, we believe that a multifactorial profiling will accurately identify genotypic alterations responsible for altered biothreat phenotype.
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