Gamma interferon signaling in oligodendrocytes is critical for protection from neurotropic coronavirus infection.
Neurotropic coronavirus induces acute encephalomyelitis and demyelination in mice. Infection of BALB/c (H-2(d)) mice expressing a dominant negative gamma interferon (IFN-gamma) receptor specifically in oligodendrocytes was examined to determine the influence of IFN-gamma signaling on pathogenesis. Inhibition of IFN-gamma signaling in oligodendrocytes increased viral load, infection of oligodendrocytes, oligodendrocyte loss, demyelination, and axonal damage resulting in increased mortality. IFN-gamma levels and the inflammatory response were not altered, although the level of tumor necrosis factor (TNF) mRNA was increased. These data indicate that IFN-gamma signaling by oligodendroglia reduces viral replication but affects both demyelination and tissue destruction in a host-specific manner.
Parra
Gabriel I
GI
Department of Neurosciences NC30, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
Bergmann
Cornelia C
CC
Phares
Timothy W
TW
Hinton
David R
DR
Atkinson
Roscoe
R
Stohlman
Stephen A
SA
D000818:Animals; D018352:Coronavirus Infections / Q000276:immunology / Q000517:prevention & control*; D003711:Demyelinating Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D004679:Encephalomyelitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D015870:Gene Expression; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000276:immunology / Q000472:pathogenicity; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D017471:Receptors, Interferon / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology
D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma