MODE OF SPREAD TO AND WITHIN THE CENTRAL-NERVOUS-SYSTEM AFTER ORAL INFECTION OF NEONATAL MICE WITH THE DA STRAIN OF THEILERS MURINE ENCEPHALOMYELITIS VIRUS

Theiler's murine encephalomyelitis virus is a neurotropic enterovirus known to cause biphasic neural disease after intracerebral inoculation into adult mice. The present study characterizes a neonatal mouse mod el with a high disease incidence for the study of the acute phase of t he pathogenesis of the DA strain of Theiler's murine encephalomyelitis virus after oral infection. The route of viral spread to and within t he central nervous system (CNS) was determined by examining the kineti cs of viral replication in various organs and by performing histopatho logical analysis. Viral antigen was detected widely in the neonatal CN S, mainly in the gray matter, and it was asymmetrical and multifocal i n its distribution, with considerable variation in lesion distribution from animal to animal. Necrotizing lesions appeared to expand by dire ct extension from infected cells to their close neighbors, with a gene ral disregard of neuroanatomical boundaries. The diencephalon showed p articular susceptibility to viral infection. Other areas of the CNS, i ncluding the cerebellum and dentate gyrus of the hippocampus, were con sistently spared. Neurons with axons extending peripherally to other o rgans or receiving direct input from the peripheral nervous system wer e not preferentially affected. The kinetics of viral replication in th e liver, spleen, and CNS and the histopathological findings indicate t hat viral entry to the CNS is via a direct hematogenous route in orall y infected neonatal mice and that the disease then progresses within t he CNS mainly by direct extension from initial foci.