Evaluating Countermeasures Against Marburg Virus Using a Mouse Model

Abstract

Animal models are key tools for understanding Marburg virus (MARV) pathogenesis and evaluating novel countermeasures. Rodents, in particular, are useful model systems because they are inexpensive and easy to house and handle in maximum containment laboratories. Unfortunately, wild-type MARV, like other filoviruses, does not cause disease in immune-competent rodents and must first be adapted to the rodent host, typically through serial passaging. In this way, mouse-adapted MARV (MA-MARV) variant Angola was generated through multiple passages in SCID mice. MA-MARV is uniformly lethal in BALB/c mice and produces many of the hallmarks associated with Marburg virus disease in humans and nonhuman primates, including robust virus replication, a dysregulated immune response, and extensive organ damage. In this chapter, we describe a protocol for inoculating mice with MA-MARV for the purpose of evaluating countermeasures.

Keywords: Animal modelling; Host-adaptation; MARV; Medical countermeasure evaluation; Mice; Pathogenesis.