p27, a novel protein in St John's Wort, that suppresses expression of HIV-1 genome

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, 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 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 p27 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 p27 forces its entry into the nucleus and diminishes the capacity of p27 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 p27 on C/EBPβ interaction with DNA. Finally, our results demonstrate that expression of p27 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 protein to control HIV-1 transcription and replication in cells associated with HIV-1 infection in the brain. © 2006 Nature Publishing Group. All rights reserved.