Bioluminescence imaging (BLI) is a technique that can be employed to quantify biological processes in living cells. When used in small animal models such as mice, BLI can provide both longitudinal and positional information regarding the biological process under investigation. Although perhaps best known for its utility in non-invasively quantifying tumor burden over time in experimental animals, BLI has also been applied in many pathogenesis models to track pathogen burden and responses to therapeutic interventions. In this chapter, we present a BLI-based method for tracing anatomical progression of lyssavirus infection in a mouse model. We also include validation methods to ensure that semiquantitative BLI data correlate well with viral load. Due to the longitudinal nature of this approach, lyssavirus pathogenesis and therapeutic intervention studies can be performed with far fewer animals than more traditional approaches, which typically require euthanasia of large animal groups at every data collection time point.
