Upon Intranasal Vesicular Stomatitis Virus Infection, Astrocytes in the Olfactory Bulb Are Important Interferon Beta Producers That Protect from Lethal Encephalitis

Previously we found that following intranasal (i.n.) infection with neurotropic vesicular stomatitis virus (VSV) type I interferon receptor (IFNAR) triggering of neuroectodermal cells was critically required to constrain intracerebral virus spread. To address whether locally active IFN-was induced proximally, we studied spatiotemporal conditions of VSV-mediated IFN- induction. To this end, we performed infection studies with IFN- reporter mice. One day after intravenous (i.v.) VSV infection, luciferase induction was detected in lymph nodes. Upon i.n. infection, luciferase induction was discovered at similar sites with delayed kinetics, whereas on days 3 and 4 postinfection enhanced luciferase expression additionally was detected in the foreheads of re-porter mice. A detailed analysis of cell type-specific IFN- reporter mice revealed that within the olfactory bulb IFN-was ex-pressed by neuroectodermal cells, primarily by astrocytes and to a lesser extent by neurons. Importantly, locally induced type I IFN triggered distal parts of the brain as indicated by the analysis of ISRE-eGFPmice which after i.n. VSV infection showed en-hanced green fluorescent protein (eGFP) expression throughout the brain. Compared to wild-type mice, IFN-/mice showe