In vivo analysis of glial cell phenotypes during a viral demyelinating disease in mice (original) (raw)
Related papers
Journal of Virology, 2008
that mimics certain pathological features of multiple sclerosis. We have examined neural cell tropism of demyelinating and nondemyelinating strains of MHV in order to determine whether central nervous system (CNS) cell tropism plays a role in demyelination. Previous studies demonstrated that recombinant MHV strains, isogenic other than for the spike gene, differ in the extent of neurovirulence and the ability to induce demyelination. Here we demonstrate that these strains also differ in their abilities to infect a particular cell type(s) in the brain. Furthermore, there is a correlation between the differential localization of viral antigen in spinal cord gray matter and that in white matter during acute infection and the ability to induce demyelination later on. Viral antigen from demyelinating strains is detected initially in both gray and white matter, with subsequent localization to white matter of the spinal cord, whereas viral antigen localization of nondemyelinating strains is restricted mainly to gray matter. This observation suggests that the localization of viral antigen to white matter during the acute stage of infection is essential for the induction of chronic demyelination. Overall, these observations suggest that isogenic demyelinating and nondemyelinating strains of MHV, differing in the spike protein expressed, infect neurons and glial cells in different proportions and that differential tropism to a particular CNS cell type may play a significant role in mediating the onset and mechanisms of demyelination. on March 22, 2016 by guest http://jvi.asm.org/ Downloaded from 5520 DAS SARMA ET AL. J. VIROL. on March 22, 2016 by guest http://jvi.asm.org/ Downloaded from FIG. 4. Colocalization of EGFP-positive cells with astrocyte marker at day 5 postinfection.
The Journal of Immunology
Theiler's murine encephalomyelitis virus induced central nervous system demyelination in susceptible strains of mice with s, q, v, p, and f H-2D alleles. We used immunoelectron microscopy to look for differential production of class II immune response gene products (Ia) within astrocytes, oligodendrocytes, microglia, and endothelial cells. Spinal cord sections from susceptible mice (B10.S and B10.ASR2) showed increased content of Ia in glial and endothelial cells. In contrast, resistant mice [B10.S(9R)] showed minimal Ia production within the CNS. The findings indicate an important role of class II immune response products on glial cells during demyelination after virus infection.
Journal of Neuroimmunology, 1981
Demyelinadon may be induced by several different pathogenetic mechanisms. We have been utilizing mouse hepatitis virus (MHV) t o study virus-induced demyalination in the central net'vous system (CNS). To learn whether the different disease phenotypes in 4-week-old mice caused by wild type (a modal for fatal encephalomyditis) or mutaf.t 158 (a model for primary demyelination), is due to an altered cellular tropism, we have developed an immnnolabeling technique to evaluate critically the localization of MHV antigens in the unique ceils of the CNS. Using mouse derived L-cells and primar.~ neuronal cells in vitro, we determined an appropriate fixative (4% paraformaldehyde and 0.5% glutaraldehyde) that both preserved MHV antigenicity and cell structure. These studies in vitro showed the presence of MHV antigens on the surface of cells.
2014
Neurotropic mouse hepatitis virus (MHV) is a member of the Coronavirus family induces hepatitis, meningitis, encephalitis, myelitis, neuritis, demyelination and axonal loss which mimics certain pathology of human neurological diseases multiple sclerosis (MS). Natural and genetically constructed recombinant MHV strains (generated by targeted RNA recombination) with differential pathological properties are used to understand the mechanisms of demyelination and concomitant axonal loss in a strain specific manner. These encompass both demyelinating (DM) and nondemyelinating (NDM) strains of MHVs, on which several comparative studies have been performed correlating the phenotypes, genomic sequences, and their pathogenicity. During acute infection, neurotropic DM strain infect a number of cell types in the CNS such as neurons, astrocytes, oligodendrocytes and microglia in the brain but in the spinal cord they preferentially infect neuron in the gray matter and oligodendrocytes and microgl...
Cell replacement therapies to promote remyelination in a viral model of demyelination
Journal of Neuroimmunology, 2010
Persistent infection of the central nervous system (CNS) of mice with the neuroadapted JHM strain of mouse hepatitis (MHV) is characterized by ongoing demyelination mediated by inflammatory T cells and macrophages that is similar both clinically and histologically with the human demyelinating disease multiple sclerosis (MS). Although extensive demyelination occurs in mice persistently-infected with MHV there is only limited remyelination. Therefore, the MHV model of demyelination is a relevant model for studying disease and evaluating therapeutic approaches to protect cells of the oligodendrocyte lineage and promote remyelination. This concept is further highlighted as the etiology of MS remains enigmatic, but viruses have long been considered as potential triggering agents in initiating and/or maintaining MS symptoms. As such, understanding mechanisms associated with promoting repair within the CNS in the context of a persistent viral infection is critical given the possible viral eitiology of MS. This review focuses on recent studies using either mouse neural stem cells (NSCs) or human oligodendrocyte progenitor cells (OPCs) derived from human embryonic stem cell (hESCs) to promote remyelination in mice persistently infected with MHV. In addition, the potential role for chemokines in positional migration of transplanted cells is addressed.
Annals of the New York Academy of Sciences, 1990
We have studied the growth and differentiation properties of oligodendrocytetype 2 astrocyte (0-2A) lineage cells isolated from mouse spinal cord in the course of demyelination and remyelination. When infected at 28 days of age with a coronavirus (murine hepatitis virus strain A59), C57BI/6N mice develop numerous foci of demyelination in the spinal cord within 3-5 weeks postinfection (wpi); extensive remyelination occurs in the following weeks.'
Virus-Induced Demyelination in Mice: “Dying Back” of Oligodendrocytes
Mayo Clinic Proceedings, 1985
Demyelination was produced in mice by intracerebral inoculation of Theiler's murine encephalomyelitis virus. The earliest ultrastructural changes occurred in the inner cytoplasmic tongues of oligodendrocytes, the most distal extension of these cells. Viral antigen was localized to glial loops that connect with myelin lamellae. This study indicates that a "dying-back" process may occur in virus-infected oligodendrocytes, which then results in demyelination.
Virology, 1995
Mice infected with the neurotropic JHM strain of mouse hepatitis virus (MHV-JHM) develop a demyelinating encephalomyelitis several weeks after infection. Astrogliosis and infiltration of inflammatory cells are prominent findings in the brains and spinal cords of infected mice. In this report, astrocytes in infected spinal cords were analyzed for expression of three pleiotropic cytokines, TNF-a, IL-1b, and IL-6; Type 2 nitric oxide synthase (iNOS); and MHC class I and II antigen. The data show that all three cytokines and iNOS are expressed by astrocytes in chronically infected spinal cords. These activated astrocytes are localized to areas of virus infection and demyelination, although most of the astrocytes expressing these proteins are not MHV-infected. MHC class I and II antigen can be detected in these spinal cords as well, but not in cells with the typical morphology of astrocytes. TNF-a, IL-6, and iNOS are also evident in the brains of mice with MHV-induced acute encephalitis, but in marked contrast to the results obtained with the chronically infected mice, most of the cells expressing these cytokines or iNOS had the morphology of macrophages or other mononuclear cells and very few appeared to be astrocytes. Additionally, astrocytes and, most likely, oligodendrocytes are infected in the spinal cords of mice with chronic demyelination. These results are consistent with a role for both viral infection of glial cells and high localized levels of proinflammatory cytokines and nitric oxide in the demyelinating process in mice infected with MHV-JHM. They also show that analogously to the human demyelinating disease, multiple sclerosis, astrocytes are a major cellular source for these cytokines in mice with chronic, but not acute disease.
Detection of visna virus antigens and RNA in glial cells in foci of demyefnation
Virology, 1985
Visna is a slow virus infection of sheep in which the characteristic pathological change is demyelination in foci of inflammation . The latter is thought to be the result of an immunopathological process directed against cellular and antigenic targets that have been difficult to define because of restricted viral gene expression . A new simultaneous detection assay is used to demonstrate viral RNA in cells identified unambiguously as oligodendrocytes and astrocytes . These cells were found in inflammatory foci. With a new strain of virus that causes a rapid form of visna in Icelandic sheep, viral antigens were demonstrated in cells in the inflammatory lesions . These findings are consistent with the postulated immunopathological mechanism of demyelination : cells that maintain intact myelin sheaths in the central nervous system are destroyed by the inflammatory response to viral antigens expressed in these cells . ce