Regulation of the HIV-1 promoter by HIF-1 and Vpr proteins

Abstract

We previously demonstrated the ability of HIV-1 Vpr protein to activate the oxidative stress pathway, thus leading to the induction of the hypoxia inducible factor 1 alpha (HIF-1). Therefore, we sought to examine the interplay between the two proteins and the impact of HIF-1 activation on HIV-1 transcription. Using transient transfection assays, we identified the optimal concentration of HIF-1 necessary for the activation of the HIV-1 promoter as well as the domain within HIF-1 responsible for this activation. Our findings indicated that activation of the HIV-1 LTR by Vpr is HIF-1 dependent. Furthermore, we showed that both Vpr and HIF-1 activate the HIV-1 promoter through the GC-rich binding domain within the LTR. Taken together, these data shed more light on the mechanisms used by Vpr to activate the HIV-1 promoter and placed HIF-1 as a major participant in this activation. © 2011 Deshmane et al; licensee BioMed Central Ltd.