The pathogenesis of lymphocytic choriomeningitis (LCM) virus infection was studied in mice by associating the development of ultrastructural changes with parallel light microscopic alterations and the build-up of viral antigen as detected by immunofluorescence. From early in the course of the disease, viral antigen was localized in the choroid plexus and ependymal epithelium and the arachnoid cells of the meninges. Typical LCM virus particles were found enmeshed in the microvillous border of the choroid plexus and ependyma as a result of budding from plasma membranes and entrapment beneath overlying macrophages and epithelial projections. These virus particles and nascent budding particles were considered the target of the terminal cell-mediated immune (CMI) response. Arenavirus inclusions were observed in the cytoplasm of the same epithelia throughout the late stages of infection, but such antigen masses were effectively sequestered. On the day before death (day 6 postinoculation), mononuclear cells invaded the choroid plexus by extravasation through the central capillary endothelium and basement lamina, and then via emperipolesis and intercellular migration through the epithelium into the cerebrospinal fluid of the ventricles. The most common invading cell type was considered a medium or large lymphocyte, but monocytes and macrophages were also present. Similar cell types invaded the ependyma and the subarachnoid space of the meninges. No cytopathology was associated with the viral infection of the choroid plexus, ependyma, or meninges, nor with the mononuclear cell influx of the CMI reaction to infection. The parenchyma of the brain remained normal throughout infection; there was no evidence of infection, inflammation, or edema. Because correspondence of the immunopathologic target site and the anatomic location of the blood-cerebrospinal fluid barrier occurred only in the choroid plexus, this organ was considered to have the central role in LCM pathogenesis. Its functional breakdown must be the proximate cause of the convulsive diatheses characteristic of the disease.
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Molecular Biology
- Clinical Biochemistry