PuSH - Publication Server of Helmholtz Zentrum München

Ludwig, E. ; Silberstein, F.C. ; van Empel, J. ; Erfle, V. ; Neumann, M. ; Brack-Werner, R.

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

J. Virol. 73, 8279-8289 (1999)
Publ. Version/Full Text Volltext PMC
Free by publisher
Open Access Green as soon as Postprint is submitted to ZB.
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.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords POLYMERASE CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; HIV-1 REV; MESSENGER-RNA; CELL-LINES; GLIAL-CELL; INTRACELLULAR TRAFFICKING; LIVING CELLS; BRAIN-CELLS; EXPRESSION
ISSN (print) / ISBN 0022-538X
e-ISSN 1098-5514
Journal Journal of Virology
Quellenangaben Volume: 73, Issue: 10, Pages: 8279-8289 Article Number: , Supplement: ,
Publisher American Society for Microbiology (ASM)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)