Journal of General Virology, Vol 79, 239-246, Copyright © 1998 by Society for General Microbiology

ARTICLES

Transcription of the human immunodeficiency virus type 1 (HIV-1) promoter in central nervous system cells: effect of YB-1 on expression of the HIV-1 long terminal repeat

BE Sawaya, K Khalili and S Amini
Center for NeuroVirology and NeuroOncology, Department of Neurology, Allegheny University of the Health Sciences, Philadelphia, PA 19102, USA.

Transcription of human immunodeficiency virus type 1 (HIV-1) is regulated by a series of host DNA-binding proteins which interact with the upstream viral promoter sequences, and the viral regulatory protein Tat which associates with TAR RNA sequences located in the leader of the viral transcript. Here we have examined the ability of the cellular protein YB-1 to modulate transcription of the HIV-1 promoter in a human astrocytic cell line (U-87MG), a neuronal cell line (SK-N-MC) and lymphoid cells (Jurkat) by transfection assay. Ectopic expression of YB- 1 in U-87MG and SK-N-MC augments basal transcriptional activity of the viral sequence located between -80 and -43, which encompasses the GC- rich motif. In accord with the previous report, in Jurkat cells YB-1- mediated activation of the HIV-1 promoter required sequences which are located further upstream from the GC-rich motif. Combined overexpression of YB-1 and the GC-rich binding protein, SP1, in the transfected cells decreased the level of activation of the viral promoter, suggesting that YB-1 and SP1 may exert negative effects on each other's function. Results from band shift assay with purified YB-1 and SP1 indicated that SP1 and YB-1 bind to the GC-rich DNA sequence in the double-stranded and single-stranded configurations, respectively. However, efficient binding of SP1 to the double-stranded GC-rich motif corresponding to the HIV-1 long terminal repeat (LTR) is diminished in the presence of YB-1. Similarly, in the presence of SP1, YB-1 loses its ability to become associated with its target single-stranded DNA probe. No evidence for direct association of YB-1 and SP1 either in the presence or in the absence of DNA was observed. These data suggest that while YB-1 stimulates expression of the LTR in central nervous system cells, the level of activity of other cellular proteins, such as SP1, may dictate binding of YB-1 to its target sequence, and therefore affect the regulatory function of this protein.

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