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4) Pathogenesis and Vaccines
Adaption of Marburg virus to rodents as a model to study viral pathogenesis
Adaption of Marburg virus to rodents as a model to study viral pathogenesis
Marburg virus causes severe febrile illness in humans and non-human primates while rodents develop only transient non-lethal disease. Passaging of the virus in guinea pigs leads to adaptive mutations, with one mutation occurring in the viral matrix protein VP40 and three in the viral polymerase L. The overall goal of the project is the characterization of the detected adaptive mutations to understand their respective contribution to the pathogenicity of the adapted MARV.
First, we analyze the mutations using reporter gene assays in cell culture systems. Next, we create recombinant viruses under BSL4 conditions, carrying single mutations or combinations of mutations. In the next step these viruses are sequenced and characterized using growth curves and electron microscopy and further methods. In the final step these viruses are analyzed in the animal model. Guinea pigs are infected under BSL4 conditions and monitored for body temperature, weight and behavior and blood samples are taken. Finally, animals are sacrificed and necropsy is performed. Virus titer in blood and organs are determined using qRT-PCR and TCID50. Furthermore, histology examination and evaluation of the pathogenicity of the viruses is performed.