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Further observations on coronavirus infection of primate CNS
R S Murray1, G Y Cai, K F Soike
1Colorado Multiple Sclerosis Center, Englewood 80110, USA.
Abstract:
Previously, we demonstrated that intracerebral (IC) inoculation of a murine coronavirus, MHV-JHM, into two species of primates can result in acute encephalomyelitis (Murray et al., 1992a). Infectious virus isolated from acutely infected animals, designated JHM-OMp1, was inoculated IC into a second group of monkeys. In this report we describe observations on the acutely infected animals and those surviving the acute infection were sacrificed at later times post-infection. Results from dual in situ hybridization/immunohistochemistry screening of tissues show that astrocytes are target cells in white matter lesions during acute infection. In animals sacrificed 150 days post-infection, areas of demyelinated gliotic lesions, prominent in the spinal cord, were seen throughout the neuraxis. No virus products were detected in these late-infection lesions.
Insights
Murine coronavirus infection causes acute encephalomyelitis in primates. Astrocytes are key targets in white matter lesions, leading to demyelination and gliosis, even without detectable virus in later stages.
Area of Science:
- Neurovirology
- Pathology
- Immunology
Background:
- Murine coronavirus (MHV-JHM) can induce acute encephalomyelitis in primates.
- Previous studies demonstrated intracerebral inoculation leads to central nervous system disease.
Purpose of the Study:
- To investigate the neuropathogenesis of MHV-JHM infection in primates.
- To identify target cells and lesion development during acute and chronic phases.
Main Methods:
- Intracerebral inoculation of MHV-JHM (JHM-OMp1 strain) into rhesus monkeys.
- Dual in situ hybridization/immunohistochemistry for viral detection and cell identification.
- Histopathological examination of brain and spinal cord tissues at acute and chronic time points.
Main Results:
- Astrocytes were identified as primary target cells within white matter lesions during acute infection.
- Demyelinated gliotic lesions were observed throughout the central nervous system, particularly in the spinal cord, 150 days post-infection.
- No viral products were detected in the chronic-phase lesions, suggesting a non-productive inflammatory or autoimmune process.
Conclusions:
- MHV-JHM infection in primates leads to astrocyte-targeted white matter damage.
- Chronic lesions characterized by demyelination and gliosis persist long after viral clearance.
- The late-stage pathology may involve immune-mediated mechanisms rather than active viral replication.