The brain parenchyma has a type I interferon response that can limit virus spread

Significance The brain parenchyma is considered to be “immune privileged” based upon differences between the innate and adaptive immune responses of the brain and those of the periphery. This work provides a clear demonstration of an innate immune response to direct infection by a virus, a response that is capable of limiting the spread of the virus along neuronal circuitry. The question of the brain parenchyma’s response to a viral infection has implications for the use of viruses as tools by neuroscientists, for vaccine development, and for potential clinical applications. Additionally, the approach used here provides a framework for further examination of the immunologic state of the brain as well as the mechanisms by which encephalitic viruses circumvent this response. The brain has a tightly regulated environment that protects neurons and limits inflammation, designated “immune privilege.” However, there is not an absolute lack of an immune response. We tested the ability of the brain to initiate an innate immune response to a virus, which was directly injected into the brain parenchyma, and to determine whether this response could limit viral spread. We injected vesicular stomatitis virus (VSV), a transsynaptic tracer, or naturally occurring VSV-derived defective interfering particles (DIPs), into the caudate–putamen (CP) and scored for an innate immune response and inhibition of virus spread. We found that the brain parenchyma has a functional type I interferon (IFN) response that can limit VSV spread at both the inoculation site and among synaptically connected neurons. Furthermore, we characterized the response of microglia to VSV infection and found that infected microglia produced type I IFN and uninfected microglia induced an innate immune response following virus injection.