Wolbachia is a bacterium that blocks virus infection in its arthropod hosts. Whilst Wolbachia blocking is being used as a strategy for interfering with the spread of Dengue virus in human populations, the mechanisms of Wolbachia-mediated viral blocking are not well characterized. A number of mechanisms have been implicated, but it is often unclear the magnitude of their contribution to the overall blocking and how broadly they apply across host-virus-Wolbachia systems. We explored what Wolbachia-mediated changes dominate the blocking phenotype to guide decisions on which large impact mechanisms to focus on for functional approaches. To do this we measured how Wolbachia impacted viral dynamics and pathogenicity in individual Drosophila hosts and combined this empirical data with a dynamical model to look at the impact of a series of parameters. Interestingly our results showed that changing several different parameters could lead to the observed impact of Wolbachia on the infection dynamics. These included: a lower rate of infection, a lower rate of viral release or a reduced number of susceptible cells. This is consistent with current thinking in the field that a combination of mechanisms may be involved in Wolbachia-mediated virus blocking and indicates that further empirical data will be important to refine the model. Our analysis indicates that it is important to understand Wolbachia’simpact on the susceptibility of individual cells. Does the presence of Wolbachia make a cell completely refractory to viral infection or is susceptibility linked to the density of Wolbachia in the cell. As we add further empirical data, the dynamical modelling approach may enable us to generate further hypothesise for testing.