The astrocyte is a target cell in mice persistently infected with mouse hepatitis virus, strain JHM

Abstract

Mouse hepatitis virus, strain JHM (MHV-JHM), causes a late onset, clinically apparent, demyelinating encephalomyelitis in 40% of suckling C57BL/6 mice born to immunized dams. Suckling mice born to unimmunized dams rapidly succumb to an acute encephalomyelitis. MHV-JHM can be isolated from the brains and spinal cords of maternal antibody-protected mice when the late onset disease becomes clinically apparent, showing that the virus must be present in these mice when they are still asymptomatic. To determine which cells of the central nervous system (CNS) were potential reservoirs for the virus during the asymptomatic period, tissue sections were assayed simultaneously by immunoperoxidase and immunofluorescence staining for the presence of viral antigen and for glial fibrillary acidic protein (GFAP), a marker for astrocytes. The results indicate that 20% (range 0-52%) of the MHV-JHM infected cells in asymptomatic mice were astrocytes. In mice symptomatic with late onset hindlimb paralysis, a higher percentage of infected cells were astrocytes. These results indicate that astrocytes are a target cell in both symptomatic and asymptomatic mice persistently infected with MHV-JHM, and suggest that the astrocyte is a potential cellular reservoir for MHV-JHM in asymptomatic mice.

Astrocytes in the tempest of multiple sclerosis

“…Persistent infection of astrocytes with HSV and close contact of infected astrocytes with T cells were detected in HSV-induced encephalitis [52,53], thus implying that astrocytes might be significant presenters of antigens in this animal model, as well. Further, astrocytes seem to be the major cellular reservoir of neurotropic MHV [54], and MHV was shown to induce both MHC class I and MHC class II molecules on astrocytes [55,56]. This relationship suggests that astrocytes are deeply involved in antigen presentation to T cells in MHV-induced demyelination of the CNS.…”

Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice

“…24 A large body of information indicates that GFAP production is an important marker of CNS injury. Pre-and postnatal viral infections including mumps and influenza, 25,26 LP-BM5 leukemia virus, 27 A59 mouse hepatitis 28,29 and HIV 30,31 cause significant astrogliosis, demonstrated by increased GFAP expression, astrocytic hypertrophy and hyperplasia. Our data are supported by various reports showing a sustained increase in GFAP protein production up to 2 months following viral insult to the developing brain.…”

Proinflammatory Cytokine Gene Induction by Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Tax in Primary Human Glial Cells

“…We speculate that CNS resident cells such as astrocytes and oligodendrocytes may be infected in vivo and that Tax1-induced cytokine gene expression further mediates neurotoxicity. Astrocytes have previously been shown to support infection by mouse hepatitis virus (MHV), HIV-1, Theiler's murine encephalomyelitis virus (TMEV), and HTLV-1 (3,5,44,55). Astrocytes interact with endothelial cells to form the BBB and may potentially also function as antigen-presenting cells (36).…”