183: Interferon regulatory factor-1 protects mice from lethal neuropathogenesis by type-I IFN-independent local antiviral effects

Interferon regulatory factor-1 (IRF-1) is a transcription factor that functions downstream of pathogen recognition receptor signalling. It has been implicated in the antiviral host responses by regulating certain antiviral genes. The study aims to determine how IRF-1 is involved in antiviral defence mechanisms which protect mice from fatal virus infections. Infection with Vesicular Stomatitis Virus (VSV) are well tolerated by wild-type mice, while those with gene disrupted IRF-1 succumb to the infection within 7 days. A comparison between the wild-type the IRF-1 −/− mice for viral replication and spread in the peripheral organs revealed no differences in viral load. Differences in the type I IFN induction were neither detectable. Since VSV is a neurotropic virus, we investigated the potential contributions of IRF-1 from VSV induced neuropathogenesis. Analysis of viral replication in the brain showed that while WT mice clear the virus from the brain high viral loads were detectable in IRF-1 −/− mice. Our results show that IRF-1 does not prevent viral entry or spread but limits viral replication and is involved in clearance of the virus from the central nervous system. Our data suggests that IRF-1 responses protect against VSV infection through an IFN-independent program in the brain which could be crucial, in situations where viruses evade immunity by the inhibition of the IFN system.