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. Marburg virus is a member of the family Filoviridae and causes severe hemorrhagic fevers in humans and nonhuman primates. It is an emerging virus and outbreaks have been reported periodically at 2-year intervals since its initial identification in 1967. Marburg is a NIH Category A select agent requiring maximum containment biosafety facilities to manipulate live virus. Virus is spread by contact with blood or body fluids from infected individuals or animals and is highly infectious. The final stages of Marburg virus infection are characterized by fever, hemorrhage, hypotensive shock with an apparent dependence on the reticuloendothelial and mononuclear phagocytic cell systems. Apart from palliative measures, there is no effective treatment for the disease. This pilot study focuses on development of a small nonhuman primate model of Marburg Hemorrhagic fever to study pathogenesis, biothreat potential, and interventions. The agent has poorly understood mechanisms of pathogenesis at both the cellular and whole animal level. Because of the shortage of non human primates currently used to study the virus, as well as the large expense required to house larger animals in biocontainment, there is a need to develop smaller non human primate models to test candidate vaccines and intervention strategies. The common marmoset has emerged as a valuable non human primate in infectious disease research. Its small size (-400 g), and its tendency to mimic human responses to infection, make it a suitable candidate for infectious disease model development. The central hypothesis is that the common marmoset (Callithrix jacchus), when inoculated with Marburg virus, will develop a disease state and immune response that is consistent with that seen in human hemorrhagic fever. Successful completion of the study will provide insight into the usefulness of the marmoset as a model for Marburg hemorrhagic fever.
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