Pathogens that gain entry into the CNS elicit a uniquely tailored response from the immune compartment by modulating cytolytic and inflammatory functions that confer viral clearance with minimal brain damage. Neurotropic viruses such as vesicular stomatitis virus (VSV) infect neurons in the olfactory epithelial barrier and pass via sensory axons directly into brain. Within the olfactory bulb, VSV-infected neurons contact a variety of CNS neurons; however, the infection rarely invades the brain. While type I interferon responses are crucial for initial viral control, little is known about how the local adaptive immune response prevents fatal viral neuroinvasion. In this study, we sought insights into how cytotoxic lymphocytes prevent distal spread of infection from the olfactory bulb. Without T cells, virus containment is compromised and VSV traverses caudally to hindbrain regions. Utilizing intravital two-photon microscopy and other techniques, we characterized the mechanism by which T cell interactions within the olfactory bulb facilitate barrier protection. Interestingly, chimeric mice deficient in MHC class I on brain-resident cells, as well as microglia-depleted mice, showed reduced antiviral T cell calcium signaling upon target cell engagement, suggesting that microglia can cross-present viral antigen and indirectly facilitate viral clearance from adjacent virally infected neurons. To understand what protective signals T cells might provide the brain, we generated VSV expressing Cre recombinase. VSV-Cre infection of floxed IFNAR or floxed IFNγR mice revealed that while continued IFNAR signaling is critical, IFNγR expression was dispensible for VSV clearance. In addition, IFNγ and perforin deficient mice are similarly resistant, while TNFα deficient animals have increased VSV susceptibility. This study has revealed a novel mechanism of T cell-mediated viral control in neurons that involves engagement of uninfected resident myeloid cells that have acquired antigen and provides barrier protection against a virus attempting to enter the CNS via the nasal route.