Genetic studies with immunocompetent mice show the importance of both T cells and gamma interferon (IFN-␥A wide variety of RNA and DNA viruses, including measles virus (MV), West Nile virus (WNV), human immunodeficiency virus, human cytomegalovirus, herpes simplex virus type 1 (HSV-1) and HSV-2, rabies virus, poliovirus, and lymphocytic choriomeningitis virus, cross the blood-brain barrier, infect the central nervous system (CNS), and cause encephalitis in mammals (3,15,26,29,34,35,75,82,85). A suitable combination of host inflammatory factors and the blood-borne viral load enables most viruses to enter the CNS. However, in the vast majority of cases, neuronal infection does not lead to overt CNS disease (82). Viral encephalitis detection rates, even when symptoms are severe, are very low (46), due in part to the poor sensitivity of the tools used to detect infection (21). However, with the increase in the number of immunocompromised individuals, whether through increasing populations of AIDS patients or pharmacologically compromised tissue transplant recipients, there has been a concomitant increase in viral encephalitis (11,77). Some viral infections, rather than being cleared by the host's immune system, result instead in high morbidity or mortality, often accompanied by severe inflammation (18,68,81). The balance between whether the adaptive immune response to a specific viral infection is protective or harmful is delicate, as many of the mechanisms that mediate inflammation in the CNS in both settings are similar (6,12,31,65).MV infection manifests itself primarily as a childhood illness with a characteristic macropapular rash. Measles is associated with high morbidity and mortality in developing countries, mostly due to a transient immunosuppression that leaves infected individuals highly susceptible to secondary infections (61). In approximately 0.1% of the cases, MV also causes CNS complications; one of these, subacute sclerosing panencephalitis (SSPE), is a progressive fatal disease. MV-associated encephalitis is one of many viral brain infections that cause high morbidity and mortality (26,34,85). The delayed pathogenesis of SSPE, including the route of viral entry into the CNS, is poorly understood (49). Although it is widely accepted that MV infection in the brain leads to complications, this is not necessarily the case, as MV mRNA is detected in the brains of 20% of individuals with no CNS pathology (33,34). It is currently hypothesized that SSPE is a result of mutated, aberrant
