Abstract
AbstractHuman immunodeficiency virus type 1 (HIV-1) is a human retrovirus and the causative agent of the acquired immunodeficiency syndrome. Genetic analysis has revealed that the HIV-1 LTR contains a potential negative regulatory element (NRE) with an E box, the recognition sequence for the helix-loop-helix (HLH) family of transcription factors. Furthermore, the upstream stimulatory factor (USF) has been implicated as a negative regulator of HIV-1 expression. Here, we report that the NRE is a composite element and that both C/EBPδ and USF can specifically bind to the NRE. The recognition sequence for C/EBPδ overlaps with the E box in the NRE of HIV-1. Competition experiments showed that either USF or C/EBPδ binds to this NRE but not both together.
Highlights
The human immunodeficiency virus type 1 (HIV-1) is a human retrovirus and the etiological agent of the acquired immunodeficiency syndrome (AIDS) [1].Several human cellular proteins regulate HIV-1 gene expression and viral replication by their interaction with the viral 5’-long terminal repeat (LTR) [2,3,4].This LTR can be divided into three major regulatory regions, based on the overall effects of each region on HIV-1 gene expression [2]
It has been shown that several proteins are able to bind to the negative regulatory element (NRE) and it has been suggested that upstream stimulatory factor (USF) could be one of the proteins binding to the E box within the NRE [6]
Based on our in vitro data, we propose a mechanism according to which USF or C/EBPδ binds to the NRE of HIV-1 LTR depending on their expression level and the cellular transcription factor context, thereby regulating the expression level of HIV genes
Summary
Several human cellular proteins regulate HIV-1 gene expression and viral replication by their interaction with the viral 5’-long terminal repeat (LTR) [2,3,4] This LTR can be divided into three major regulatory regions, based on the overall effects of each region on HIV-1 gene expression [2]. One of them is the region located between nucleotide positions -167 and -423, which has a negative effect on the rate of transcription in vivo and in vitro [5] This negative regulatory region contains a number of recognition sequences for cellular transcription factors [2, 4]. It has been shown that several proteins are able to bind to the NRE and it has been suggested that upstream stimulatory factor (USF) could be one of the proteins binding to the E box within the NRE [6]
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