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p27SJ, a novel protein in St John's Wort, that suppresses expression of HIV-1 genome

Abstract

Transcription of the HIV-1 genome is controlled by the cooperation of viral regulatory proteins and several host factors which bind to specific DNA sequences within the viral promoter spanning the long terminal repeat, (LTR). Here, we describe the identification of a novel protein, p27SJ, present in a laboratory callus culture of Hypericum perforatum (St John's Wort) that suppresses transcription of the HIV-1 genome in several human cell types including primary culture of microglia and astrocytes. p27SJ associates with C/EBPβ, a transcription factor that regulates expression of the HIV-1 genome in macrophages and monocytic cells, and the viral transactivator, Tat. The association of p27SJ with C/EBPβ and Tat alters their subcellular localization, causing their accumulation in the perinuclear cytoplasmic compartment of the cells. Fusion of a nuclear localization signal to p27SJ forces its entry into the nucleus and diminishes the capacity of p27SJ to suppress Tat activity, but does not alter its ability to suppress C/EBPβ activation of the LTR. Results from binding assays showed the inhibitory effect of p27SJ on C/EBPβ interaction with DNA. Finally, our results demonstrate that expression of p27SJ decreases the level of viral replication in HIV-1-infected cells. These observations suggest the potential for the development of a therapeutic advance based on p27SJ protein to control HIV-1 transcription and replication in cells associated with HIV-1 infection in the brain.

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Acknowledgements

We thank past and present members of the Center for Neuorovirology for their support, insightful discussion, and sharing of ideas and reagents. We appreciate the assistance of the Protein Core Facility of the Wistar Institute (Philadelphia, PA, USA) in protein sequencing. We are grateful to MK White for critical reading of this manuscript and his helpful comments. We also thank C Schriver for editorial assistance. This work was made possible by grants awarded by the NIH to SA, BES, and KK.

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Correspondence to K Khalili.

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Accession numbers of p27SJ in GenBank Hypericum perforatum p27SJ mRNA, partial cdsgi57868105gbAY866430.1[57868105]p27SJ [Hypericum perforatum]gi57868106gbAAW57408.1[57868106]

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Darbinian-Sarkissian, N., Darbinyan, A., Otte, J. et al. p27SJ, a novel protein in St John's Wort, that suppresses expression of HIV-1 genome. Gene Ther 13, 288–295 (2006). https://doi.org/10.1038/sj.gt.3302649

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  • DOI: https://doi.org/10.1038/sj.gt.3302649

Keywords

  • HIV-1
  • gene expression
  • St John's Wort
  • viral replication
  • Tat
  • Hypericum perforatum
  • C/EBPβ

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