The mouse model of HeV encephalitis lends itself well to pathogenesis studies of this type as the animals do not succumb to fulminating systemic infection prior to the establishment of significant neuropathology, the CNS lesions develop over a sufficiently long period of time that their progression can be monitored in considerable detail, and high levels of genome persist in brain in spite of virus neutralizing antibody, albeit that it occurs at low level. A particular advantage is that mice are small and comparatively easy to handle at BSL4 and there is an established library of available reagents for neuropathogenetic studies. HeV infection has also been established in two strains of mice, BALB/c and C57BL/6, providing investigators with the opportunity to employ transgenic mouse systems on two genetic backgrounds to examine disease processes, particularly with regard to the immune response in CNS infection.