The development of a reverse genetics system for Machupo virus

The etiologic agent of Bolivian hemorrhagic fever (BHF), Machupo virus (MACV), is a highly lethal viral pathogen with no approved vaccine or therapeutic to limit infection or outbreaks. Following implementation of rodent population controls after the initial outbreak, no cases of BHF were reported from 1976 to 1993. Reports in the last five years from the endemic region have identified a surge in reported cases and deaths from the disease. Since then, very little characterization or research of MACV has been accomplished. In this research, I describe the development of two major tools for studying MACV: The development of a mini-genome for both the small and large segments, and the establishment of a reverse genetics system and rescue of a recombinant MACV. Using these tools, I present the first modern in vitro characterization of MACV, the development of a novel and lethal murine animal model, and the generation of a rationally attenuated MACV.