Role of type I and type II interferon responses in recovery from infection with an encephalitic flavivirus

We have investigated the contribution of the interferon (IFN)-alpha/beta system, IFN-gamma and nitric oxide to recovery from infection with Murray Valley encephalitis virus, using a mouse model for flaviviral encephalitis where a small dose of virus was administered to 6-week-old wild-type and gene knockout animals by the intravenous route. We show that a defect in the IFN-alpha/beta responses results in uncontrolled extraneural virus growth, rapid virus entry into the brain and 100 % mortality. In contrast, mice deficient in IFN-gamma or nitric oxide production display an only marginally increased susceptibility to infection with the neurotropic virus.