CHARACTERIZATION OF NONHUMAN PRIMATE LUNG AND BRONCHOALVEOLAR LAVAGE SAMPLES BY FLOW CYTOMETRY FOLLOWING AEROSOL CHALLENGE WITH VIRAL PATHOGENS
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Type of Work71 pages
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Outbreaks of several highly pathogenic viruses such as Ebola virus, Marburg virus, and Nipah virus occur periodically in some parts of the world. Because these viruses are highly infectious and associated with high mortality rates, there is some concern that one or more of them could be developed as a bioweapon. In order to be able to effectively treat victims of outbreaks as well as understand and counter the possibility of one of these agents being used in an act of bioterrorism, they are studied extensively in specialized labs throughout the world. Nonhuman primates are frequently used as models in the study of high consequence viral pathogens because of their similarity to humans. Typically, a nonhuman primate species is selected as a model for each virus based on similarity of disease course to that in humans. In addition to species selection, a challenge route must be selected according to the specific goals of the proposed study. In spite of there not having ever been a documented case of a human contracting any of these viruses via aerosol transmission, aerosol challenge is common in these types of studies due to concerns that one of these viruses could be altered in some way, as a bioterrorism agent, that would allow it to infect via aerosols. Since the lungs are the primary challenge site in an aerosol infection, valuable information could be gleaned from monitoring changes in the lungs. Unfortunately, there is a scarcity in the published literature of information about the normal lung environment in nonhuman primate (NHP) species. In order to determine abnormalities that occur due to infection and pathogenesis it is important to first determine what that environment typically looks like in a normal uninfected individual of the same species. In this work, the lung environment in normal rhesus macaques and African Green monkeys was characterized through the use of flow cytometric analysis of both lung tissues and bronchoalveolar lavage. Normal values for leukocyte composition were determined via 16-color flow cytometry and then the same assay was used to evaluate the lung environment of rhesus macaques infected with Ebola virus and African Green monkeys that had been infected with Nipah virus via aerosol challenge.
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