Phenotypic characterisation and infection of ovine microglial cells with Maedi-Visna Virus

Maedi-Visna Virus (MW) infection of the central nervous system (CNS) results in pathological changes, the mechanisms of which are poorly understood. MW preferentially infects cell of the monocyte/macrophage lineage in vivo. The neuroparenchymal microglial cells are the resident tissue macrophages in the CNS and therefore likely targets for MVV infection. However, no information is currently available on the susceptibility of these cells to MW infection or their contribution to neuropathological changes as a result of MW infection. Highly enriched primary ovine microglial cell cultures were set up from brain tissues of lambs. These cells were amoeboid or bipolar with spikes, a morphology consistent with microglial cells of other species, and stained positive for CD1, CD11a, CD11c, CD14, MHC-class I, MHC-class II, and beta-N-acetyl galactose, but not with markers of astrocytes or oligodendrocytes. These sheep microglial cells were permissive for MVV infection. Productive MVV infection resulted in selective transcriptional upregulation of the pro-inflammatory cytokines TNF alpha and IL-6, In contrast, there was no change in levels of transcripts for TGF beta 1, IL-1 beta, GM-CSF, IL-10, or IL-12. These data provide the first evidence that ovine microglial cells can support productive infection with MW, and that this leads to a selective upregulation of proinflammatory cytokines. These may contribute to visna neuropathology.