Sequence of murine coronavirus JHM induced neuropathological changes in rats.

Infection of 21-25-day-old rats with the murine coronavirus JHM was followed either by an acute encephalomyelitis (AE) or subacute demyelinating encephalomyelitis (SDE). The major neuropathological finding in AE, which developed within 6-12 days p.i. consisted of necrotizing lesions distributed mainly in the grey matter of the central nervous system (CNS). SDE developed 14-30 days p.i. and affected rats revealed lesions of primary demyelination with predilection sites in the white matter. The time-course for the development of lesions, virus replication and neutralizing antiviral antibody production within the first 3 weeks p.i. were studied. Within the first 2 weeks p.i., most rats showed no clinical signs but nevertheless revealed lesions typical of AE. In parallel to these neuropathological changes infectious virus could be isolated from brain and spinal cord. However, coinciding with multiplication of neutralizing JHM antibodies 10-12 days after infection no infectious virus was recoverable from CNS material. At this time many of the clinically healthy rats showed demyelinating lesions which were located at the typical predilection sites of SDE. These observations indicated that SDE was preceded by clinically silent AE lesions.