Effects of extracellular human immunodeficiency virus type 1 Vpr protein in primary rat cortical cell cultures

Recent evidence suggests that HIV-1 Vpr exists in soluble form in the serum and cerebrospinal fluid (CSF). Further, its abundance in the bloodstream, and the CSF, and its activity on other cell types suggest that it could hav e an effect on brain activity. Using mixed embryonic rat brain cultures as a model to examine the effects of physiological concentrations of extracell ular Vpr protein, Vpr-induced cell death was observed. We also observed sim ilar Vpr-induced effects in enriched primary cortical rat astrocytes, as we ll as in the C6 glioma cell line. Vpr-induced cell death observed in the as trocytic cells appeared to be caused primarily by a necrotic mechanism, alt hough a few apoptotic nuclei were also present. We did not observe Vpr-indu ced effects on any primary cortical neurons, although we did observe Vpr-in duced cell death in hippocampal neurons and astrocytes. Finally, we observe d no cell cycle effects due to extracellular Vpr protein. This data points out that different cell types are affected by the toxic effects of extracel lular Vpr protein, and that differential toxic effects of extracellular Vpr protein are observed in similar cell types.