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.