Neurons and oligodendrocytes in the mouse brain differ in their ability to replicate Semliki Forest virus

Semliki Forest virus (SFV) provides an experimental model of acute virus encephalitis and virus-induced demyelinating disease. Two marker viruses expressing fluorescent proteins as part of the replicase or the structural open reading frame were used to evaluate virus replication in cells of the adult mouse brain. Both marker viruses established a high-titer infection in the adult mouse brain. As determined by location, morphology, and immunostaining with neural cell type-specific phenotypic markers, both viruses infected neurons and oligodendrocytes but not astrocytes. Determination of eGFP expression from either the replicase or the structural open-reading frame coupled with immunostaining for either the virus structural protein or the virus nonstructural protein-3 readily distinguished cells at early and late stages of infection. Neurons but not oligodendrocytes rapidly down-regulated virus replication. Rapid down-regulation of virus replication was also observed in mature but not immature primary cultures of rat hippocampal neurons. This study demonstrates for the first time that in vivo central nervous system (CNS) cells differ in their ability to suppress alphavirus replication.