Anterograde axonal transport and spread of virus from neurons to oligodendrocytes have been documented, but retrograde axonal spread of virus from nerve ending to neural cell body also needs to be considered. Earlier studies suggested that MHV strains may spread via retrograde axonal transport (6, 7) , but the molecular mechanisms mediating such transport are not well defined. In the optic nerve, the parental demyelinating strain MHV-A59 causes inflammation, demyelination, and axonal loss (ie, optic neuritis), in contrast to the nondemyelinating MHV-2 strain (8) . Whether MHVinduced optic neuritis is dependent on retrograde axonal transport of viral particles or is due to local traumatic disruption of the intracranial portion of retinal ganglion cell (RGC) axons during inoculation is not known. Moreover, the immune response in MHV recombinant strain optic neuritis has not been well characterized. Here, we compared the incidence and phenotype of optic neuritis after inoculation with RSA59 and RSMHV2 and assessed the ability of spike protein to facilitate retrograde axonal transport and induce optic neuritis.