Lineage directed differentiation of human brain derived progenitor cells alters JC Virus and HIV-1 fate of infection: Implications of neuropathogenesis

We have identified, isolated, and continually propagated neural progenitor cells from the developing human brain. These cells, NPCs, can be directed to multiple lineage pathways including neurons, astrocytes and oligodendrocytes by introduction of different factors into the cell culture medium. Treatment of NPCs with either the human polyomavirus, JCV, or HIV-1, resulted in only a small fraction of the these cells showing infection. However, either at the time of delivery of virus or after 4 or more days after virus treatment, if the cells were directed to an astrocyte lineage, there was a substantial increase of virus synthesis indicating differentiation induced activation of either JCV or HIV-1. Differentiation toward a neuronal lineage reduced viral synthesis quickly until the infection was eliminated. For JCV infection, molecular factors that are responsible for successful infection were altered during the course of lineage directed infection. In brain tissue of pediatric cases of AIDS encephalitis, HITV-1 infection was identified in nestin positive cells in the subventricular zone and in the hippocampus. These viruses may target neural progenitor cells in the brain contributing to the pathogenesis of neurodegeneration.