Recombinant MHV strains RSA59 (demyelinating strain; DM) and RSMHV2 (nondemyelinating strain; NDM) are isogenic except for the spike gene, which encodes the host attachment spike glycoprotein. Studies of these strains have elucidated mechanisms of axonal loss and demyelination (3) . RSA59 and RSMHV2 both cause hepatitis, encephalitis, and meningitis after intracranial inoculation. However, they differ in their ability to induce macrophage infiltration and subsequent demyelination and axonal loss in spinal cord (2) . There is a lack of viral antigen spread and subsequent inflammation extending into spinal cord white matter after intracranial infection with the NDM strain, whereas there is extensive macrophage-mediated white matter pathology secondary to DM strain infection. Thus, the spike protein plays a critical role in anterograde axonal transport of viral particles, an important mechanism mediating axonal damage and demyelination (2, 4) . Because both strains cause encephalitis after transcranial inoculation, the differences in spike protein between DM and NDM strains do not impair viral entry; however, differential neural cell tropism may contribute to the mechanism of demyelination (2, 4, 5) . Infection of brain neurons and oligodendrocytes occurs on inoculation with either strain, whereas in the spinal cord, oligodendrocyte infection is only seen with the DM strain. This is likely due to the route by which the virus gains access to white matter, that is, spinal cord infection does not occur as a result of direct trauma, whereas transcranial inoculation results in traumatic disruption of the brain gray-white matter interface. Viral particles that would require anterograde axonal transport from infected neurons to reach myelin are able to gain direct access to the myelin sheath and spread proximally to oligodendrocyte cytoplasm.