Once we had established that IL-1 contributed to acute pathology after intramuscular VSV inoculation, the most important question to pursue was whether IL-1 would be required for control of VSV replication in vivo, and for the induction of immune responses to the VSV vector. If IL-1 were not required for control of virus replication, or for generation of protective immune responses, then that would suggest that engineering rVSV vectors to suppress IL-1 production and/or signaling would be a rational approach to reducing rVSV associated pathology.