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Journal of Virology, October 1999, p. 8279-8289, Vol. 73, No. 10
0022-538X/99/$04.00+0

Diminished Rev-Mediated Stimulation of Human Immunodeficiency Virus Type 1 Protein Synthesis Is a Hallmark of Human Astrocytes

Eva Ludwig, Francesca Ceccherini- Silberstein, Jutta van Empel, Volker Erfle, Markus Neumann, and Ruth Brack-Werner*

Institute of Molecular Virology, GSF-National Research Center for Environment and Health, D-85764 Neuherberg, Germany

Received 4 March 1999/Accepted 16 May 1999

Astrocytes are target cells for human immunodeficiency virus type 1 (HIV-1) in the central nervous system with attenuated virus replication in vivo and in vitro. In infected astrocytes, viral gene expression is restricted mainly to nonstructural (early) viral components like Nef, suggesting inhibition of Rev-dependent posttranscriptional processes in these cells. Because of the heterogeneity of astrocytic cells, the objective of this study was to determine whether restriction of HIV-1 Rev-associated activities is a common property of human astrocytes. To this end, we compared the trans activation capacity and intracellular distribution of Rev in four astrocytoma cell lines previously shown to be infectible by HIV-1 and in primary human fetal astrocytes from different sources with Rev-permissive nonglial control cell 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 control cells. Nuclear accumulation of Rev in astrocytes was restored by blocking export of Rev. The trans activation capacity and nuclear localization of Tat were not affected in astrocytes. These results demonstrate that inhibition of Rev-dependent posttranscriptional regulation of HIV-1 is a hallmark of human astrocytes and may contribute to suppression of HIV-1 production in these HIV-1 reservoirs. Astrocytes constitute the first example of a human cell type showing an impaired Rev response, indicating that posttranscriptional control of HIV-1 gene expression can be modulated in a cell-dependent manner.

* Corresponding author. Mailing address: Institute of Molecular Virology, GSF-National Research Center for Environment and Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany. Phone: 49-89-3187 2923. Fax: 49-89-3187 3329. E-mail: brack{at}gsf.de.

Journal of Virology, October 1999, p. 8279-8289, Vol. 73, No. 10
0022-538X/99/$04.00+0


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