Diminished Rev-mediated stimulation of human immunodeficiency virus type 1protein synthesis is a hallmark of human astrocytes

Astrocytes are target cells for human immunodeficiency virus type 1 (HIV-1) in the central nervous system with attenuated virus replication in vivo an d in vitro. In infected astrocytes, viral gene expression is restricted mai nly to nonstructural (early) viral components like Nef, suggesting inhibiti on of Rev-dependent posttranscriptional processes in these cells. Because o f the heterogeneity of astrocytic cells, the objective of this study was to determine whether restriction of HIV-1 Rev-associated activities is a comm on property of human astrocytes. To this end, we compared the trans activat ion capacity and intracellular distribution of Rev in four astrocytoma cell lines previously shown to be infectible by HIV-1 and in primary human feta l astrocytes from different sources with Rev-permissive nonglial control ce ll lines. In all astrocytic cell cultures, the Rev response was reduced to about 10% of that of Rev-permissive control cells. Rev was apparent both in cytoplasmic and in nuclear compartments of living astrocytes, in contrast to the typical nuclear and/or nucleolar localization of Rev in permissive c ontrol cells. Nuclear accumulation of Rev in astrocytes was restored by blo cking export of Rev. The trans activation capacity and nuclear localization of Tat were not affected in astrocytes. These results demonstrate that inh ibition of Rev-dependent posttranscriptional regulation of HIV-1 is a hallm ark of human astrocytes and may contribute to suppression of HIV-1 producti on in these HIV-1 reservoirs. Astrocytes constitute the first example of a human cell type showing an impaired Rev response, indicating that posttrans criptional control of HIV-1 gene expression can be modulated in a cell-depe ndent manner.