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J. Virol., Apr 1995, 2159-2167, Vol 69, No. 4
Copyright © 1995, American Society for Microbiology

Restriction of human immunodeficiency virus type 1 production in a human astrocytoma cell line is associated with a cellular block in Rev function

M Neumann, BK Felber, A Kleinschmidt, B Froese, V Erfle, GN Pavlakis and R Brack- Werner
GSF-Institute of Molecular Virology, Oberschleissheim, Germany.

Chronically human immunodeficiency virus type 1 (HIV-1) strain IIIB- infected human TH4-7-5 astrocytoma cells show low-level virus production. Cocultivation of TH4-7-5 cells with myelomonocytic cells led to active virus production in these target cells after a lag period, indicating cell-determined restriction of virus replication in the glial cells. HIV-1 transcript patterns of TH4-7-5 cells contained only a small proportion of Rev-dependent mRNA species, mimicking a Rev- negative phenotype despite the presence of rev mRNAs and protein. Sequencing of the single provirus integrated in TH4-7-5 cells demonstrated that the rev gene and the Rev-responsive element are intact. These results suggested inhibited function of the Rev- regulatory unit in these astrocytoma cells. Transfection of TH4-7-5 cells with a Rev expression plasmid resulted in weak or no induction of proviral p24gag antigen levels compared with the dramatic increase observed in Rev-permissive HeLa cells. Immunofluorescence analysis of TH4-7-5 cells transfected with a rev-expressing plasmid revealed prominent cytoplasmic and nuclear-nucleolar localization of Rev, in contrast to the predominant nuclear-nucleolar localization pattern of Rev in HeLa cells. We conclude that restriction of virus production in TH4-7-5 cells is at least partially due to a block in Rev-dependent posttranscriptional regulation of HIV expression.

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