1. ¹Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA, USA
2. ²Department of Plant Physiology and Microbiology, Yerevan State University, Yerevan, Armenia

Correspondence: Dr K Khalili, Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900 North 12th Street, 015-96, Room 203, Philadelphia, PA 19122, USA. E-mail: kamel.khalili@temple.edu

Received 5 April 2005; Revised 21 June 2005; Accepted 11 August 2005; Published online 27 October 2005.

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, p27^SJ, 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. p27^SJ associates with C/EBP, a transcription factor that regulates expression of the HIV-1 genome in macrophages and monocytic cells, and the viral transactivator, Tat. The association of p27^SJ with C/EBP and Tat alters their subcellular localization, causing their accumulation in the perinuclear cytoplasmic compartment of the cells. Fusion of a nuclear localization signal to p27^SJ forces its entry into the nucleus and diminishes the capacity of p27^SJ to suppress Tat activity, but does not alter its ability to suppress C/EBP activation of the LTR. Results from binding assays showed the inhibitory effect of p27^SJ on C/EBP interaction with DNA. Finally, our results demonstrate that expression of p27^SJ 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 p27^SJ protein to control HIV-1 transcription and replication in cells associated with HIV-1 infection in the brain.