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Is Required for Viral Clearance from Central Nervous System Oligodendroglia1
,
Departments of
*
Molecular Microbiology and Immunology,
Neurology, and
Pathology, University of Southern California School of Medicine, Los Angeles, CA 90033
Infection of the central nervous system (CNS) by the JHM strain of
mouse hepatitis virus (JHMV) is a rodent model of the human
demyelinating disease multiple sclerosis. The inability of effective
host immune responses to eliminate virus from the CNS results in a
chronic infection associated with ongoing recurrent demyelination. JHMV
infects a variety of CNS cell types during the acute phase of infection
including ependymal cells, astrocytes, microglia, oligodendroglia, and
rarely in neurons. Replication within the majority of CNS cell types is
controlled by perforin-dependent virus-specific CTL. However,
inhibition of viral replication in oligodendroglia occurs via a
perforin-independent mechanism(s). The potential role for IFN-
as
mediator controlling JHMV replication in oligodendroglia was examined
in mice deficient in IFN- secretion (IFN-0/0 mice).
IFN-0/0 mice exhibited increased clinical symptoms and
mortality associated with persistent virus, demonstrating an inability
to control replication. Neither antiviral Ab nor CTL responses were
diminished in the absence of IFN-, although increased IgG1 was
detected in IFN-0/0 mice. Increased virus Ag in the
absence of IFN- localized almost exclusively to oligodendroglia and
was associated with increased CD8+ T cells localized within
white matter. These data suggest that although perforin-dependent CTL
control virus replication within astrocytes and microglia, which
constitute the majority of infected CNS cells, IFN- is critical for
control of viral replication in oligodendroglia. Therefore, different
mechanisms are used by the host defenses to control virus replication
within the CNS, dependent upon the phenotype of the targets of virus
replication.
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B. P. Chen, W. A. Kuziel, and T. E. Lane Lack of CCR2 Results in Increased Mortality and Impaired Leukocyte Activation and Trafficking Following Infection of the Central Nervous System with a Neurotropic Coronavirus J. Immunol., October 15, 2001; 167(8): 4585 - 4592. [Abstract] [Full Text] [PDF]
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C. C. Bergmann, C. Ramakrishna, M. Kornacki, and S. A. Stohlman Impaired T Cell Immunity in B Cell-Deficient Mice Following Viral Central Nervous System Infection J. Immunol., August 1, 2001; 167(3): 1575 - 1583. [Abstract] [Full Text] [PDF]
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M. T. Liu, D. Armstrong, T. A. Hamilton, and T. E. Lane Expression of Mig (Monokine Induced by Interferon-{{gamma}}) Is Important in T Lymphocyte Recruitment and Host Defense Following Viral Infection of the Central Nervous System J. Immunol., February 1, 2001; 166(3): 1790 - 1795. [Abstract] [Full Text] [PDF]
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M. T. Liu, B. P. Chen, P. Oertel, M. J. Buchmeier, D. Armstrong, T. A. Hamilton, and T. E. Lane Cutting Edge: The T Cell Chemoattractant IFN-Inducible Protein 10 Is Essential in Host Defense Against Viral-Induced Neurologic Disease J. Immunol., September 1, 2000; 165(5): 2327 - 2330. [Abstract] [Full Text] [PDF]
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G. F. Wu, L. Pewe, and S. Perlman Coronavirus-Induced Demyelination Occurs in the Absence of Inducible Nitric Oxide Synthase J. Virol., August 15, 2000; 74(16): 7683 - 7686. [Abstract] [Full Text]
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G. F. Wu, A. A. Dandekar, L. Pewe, and S. Perlman CD4 and CD8 T Cells Have Redundant But Not Identical Roles in Virus-Induced Demyelination J. Immunol., August 15, 2000; 165(4): 2278 - 2286. [Abstract] [Full Text] [PDF]
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N. W. Marten, S. A. Stohlman, R. D. Atkinson, D. R. Hinton, J. O. Fleming, and C. C. Bergmann Contributions of CD8+ T Cells and Viral Spread to Demyelinating Disease J. Immunol., April 15, 2000; 164(8): 4080 - 4088. [Abstract] [Full Text] [PDF]
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B. Parra, M. T. Lin, S. A. Stohlman, C. C. Bergmann, R. Atkinson, and D. R. Hinton Contributions of Fas-Fas Ligand Interactions to the Pathogenesis of Mouse Hepatitis Virus in the Central Nervous System J. Virol., March 1, 2000; 74(5): 2447 - 2450. [Abstract] [Full Text]
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G. F. Wu and S. Perlman Macrophage Infiltration, but Not Apoptosis, Is Correlated with Immune-Mediated Demyelination following Murine Infection with a Neurotropic Coronavirus J. Virol., October 1, 1999; 73(10): 8771 - 8780. [Abstract] [Full Text] [PDF]
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C. C. Bergmann, J. D. Altman, D. Hinton, and S. A. Stohlman Inverted Immunodominance and Impaired Cytolytic Function of CD8+ T Cells During Viral Persistence in the Central Nervous System J. Immunol., September 15, 1999; 163(6): 3379 - 3387. [Abstract] [Full Text] [PDF]
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