Regulation of the HIV-1 promoter by HIF-1α and Vpr proteins.
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-1α). Therefore, we sought to examine the interplay between the two proteins and the impact of HIF-1α activation on HIV-1 transcription. Using transient transfection assays, we identified the optimal concentration of HIF-1α necessary for the activation of the HIV-1 promoter as well as the domain within HIF-1α responsible for this activation. Our findings indicated that activation of the HIV-1 LTR by Vpr is HIF-1α dependent. Furthermore, we showed that both Vpr and HIF-1α 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-1α as a major participant in this activation.
Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, USA.
Satish L
SL
Deshmane
Shohreh
S
Amini
Satarupa
S
Sen
Kamel
K
Khalili
Bassel E
BE
Sawaya
D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1