Cellular RelB interacts with the transactivator Tat and enhance HIV-1 expression

Meng Wang,Yu Chen,Jian Wang,Wei Yang,Wentao Qiao,Juan Tan

doi:10.1186/s12977-018-0447-9

Abstract

BackgroundHuman immunodeficiency virus type 1 (HIV-1) Tat protein plays an essential role in HIV-1 gene transcription. Tat transactivates HIV-1 long terminal repeat (LTR)-directed gene expression through direct interactions with the transactivation-responsive region (TAR) element and other cis elements in the LTR. The TAR-independent Tat-mediated LTR transactivation is modulated by several host factors, but the mechanism is not fully understood.ResultsHere, we report that Tat interacts with the Rel homology domain of RelB through its core region. Furthermore, RelB significantly increases Tat-mediated transcription of the HIV-1 LTR and viral gene expression, which is independent of the TAR. Both Tat and RelB are recruited to the HIV-1 promoter, of which RelB facilitates the recruitment of Tat to the viral LTR. The NF-κB elements are key to the accumulation of Tat and RelB on the LTR. Knockout of RelB reduces the accumulation of RNA polymerase II on the LTR, and decreases HIV-1 gene transcription. Together, our data suggest that RelB contributes to HIV-1 transactivation.ConclusionsOur results demonstrate that RelB interacts with Tat and enhances TAR-independent activation of HIV-1 LTR promoter, which adds new insights into the multi-layered mechanisms of Tat in regulating the gene expression of HIV-1.

Highlights

Human immunodeficiency virus type 1 (HIV-1) Tat protein plays an essential role in HIV-1 gene transcription
HIV‐1 Tat interacts with RelB To identify proteins that interact with HIV-1 Tat, we performed a yeast two-hybird screening with a human universal cDNA library as the prey and with HIV-1 Tat as the bait
We report that Tat interacts with RelB, and they are recruited to the long terminal repeat (LTR), which leads to increased recruitment of RNA Pol II to the LTR and greater transcription of viral genes (Fig. 10)

Summary

Introduction

Human immunodeficiency virus type 1 (HIV-1) Tat protein plays an essential role in HIV-1 gene transcription. Tat transactivates HIV-1 long terminal repeat (LTR)-directed gene expression through direct interactions with the transactivation-responsive region (TAR) element and other cis elements in the LTR. Tat potently transactivates HIV-1 LTRdirected gene expression by directly interacting with the nascent RNA stem-loop known as the transactivationresponsive region (TAR) and promoting transcription elongation [6]. NF-κB binding sites are found in the enhancer region of all primate lentiviral LTRs, the number may vary between different subtypes of HIV-1. Human immunodeficiency virus type 2 (HIV-2) and the A/E recombinant of HIV-1 contain a single NF-κB binding site. Subtype C strains typically contain three binding sites of NF-κB in their enhancer regions [17, 18]. Earlier studies have shown that Tat can directly bind to the NF-κB binding sites [21, 22] and activate NF-κB via physical interactions with IκBα and RelA at the initiation step of transcription [23]

Methods

Results

Discussion

Conclusion