Spread of MHV-JHM from nasal cavity to white matter of spinal cord. Transneuronal movement and involvement of astrocytes.

C57B1/6 mice infected intranasally with mouse hepatitis virus, strain JHM (MHV-JHM) develop hindlimb paralysis with histological evidence of demyelination several weeks after inoculation. Virus must spread from the site of inoculation, the nasal cavity, to the site of disease, the white matter of the spinal cord. It has been shown previously that after intranasal inoculation, virus enters the brain via the olfactory nerve and spreads to infect many of its neuroanatomic connections within the central nervous system (CNS). In this report, it is shown that virus infecting the spinal cord is first detected in the gray matter, with spread occurring to the white matter soon thereafter. Astrocytes are heavily infected during the process of spread from the gray to the white matter of the spinal cord. Since astrocytes are in intimate contact with neuronal synapses and are themselves connected via gap junctions, these results suggest that astrocytes may be a conduit for the spread of virus in these mice. Astrocytes provide factors for the proliferation and survival of oligodendrocytes, and widespread infection of these cells might contribute to the demyelinating process eventually observed in these mice. Additionally, since virus first appears at specific locations in the spinal cord, it should be possible to determine the source of the virus infecting the cord. While the results are not definitive, the data are most consistent with virus spreading from the ventral reticular formation to the gray matter of the cervical spinal cord.