CD8+ T-cells play a crucial role in eradicating viral infections. The focus of this project is two-fold. First, to study general in vivo mechanisms of virus - host interactions and second, to understand how primary and memory T-cells respond to virus infection. Despite the importance of T-cells, we do not yet fully understand the induction of a CD8+ T-cell responses and the generation of CD8+ T-cell memory to virus infection. For viruses in which traditional vaccine approaches have not been successful, it is hoped that induction of CD8+ T-cell memory will enhance immunity. To induce optimal CD8+ T-cell responses to vaccines it is necessary to understand how primary CD8+ T-cells are stimulated. This project aims to address questions related to the optimal activation of T cell immunity following primary and secondary virus infection by studying several viruses and different routes of infection. In 2014, we have continued our examination of poxvirus skin infections and the distinct roles for and interaction of innate and adaptive immune cells and effector mechanisms in virus clearance.