Pseudomonas DING proteins as human transcriptional regulators and HIV-1 antagonists

Andrew Suh,Ken Scott,Valentin Le Douce,Christian Schwartz,Olivier Rohr

doi:10.1186/1743-422x-10-234

Abstract

BackgroundAnti-HIV-1 therapy depends upon multiple agents that target different phases of the viral replication cycle. Recent reports indicate that plant and human DING proteins are unique in targeting viral gene transcription as the basis of their anti-HIV-1 therapy.MethodsTwo cloned DING genes from Pseudomonas were transiently expressed in human cells, and effects on NFκB-mediated transcription, HIV-1 transcription, and HIV-1 production were measured.ResultsBoth DING proteins elevated NFκB-mediated transcription. In microglial cells, one protein, from P. aeruginosa PA14, suppressed HIV-1 transcription; the other protein, from P. fluorescens SBW25, was inactive. The PA14DING protein also reduces HIV-1 production in microglial cells.ConclusionsStructural differences between the two DING proteins highlight regions of the PA14DING protein essential to the anti-HIV-1 activity, and may guide the design of therapeutic agents.

Highlights

Anti-HIV-1 therapy depends upon multiple agents that target different phases of the viral replication cycle
In order to ensure the intracellular localisation of Pseudomonas DING proteins and test their effect on NFκB transcription in a cell-based reporter assay, DING genes from P. aeruginosa PA14 (PA14DING) and P. fluorescens SBW25 (PfluDING) were cloned into human expression plasmids
In order to control for the over-expression of a Pseudomonas phosphate binding protein, PstS genes from P. aeruginosa PA14 and P. fluorescens SBW25 were cloned into a human expression vector and tested for their effect on NFκB-mediated transcription

Summary

Introduction

Anti-HIV-1 therapy depends upon multiple agents that target different phases of the viral replication cycle. Recent reports indicate that plant and human DING proteins are unique in targeting viral gene transcription as the basis of their anti-HIV-1 therapy. The synovial stimulatory protein, secreted by rheumatoid arthritis synovial fibroblasts, induces an inflammatory response in synovial T-cells and has a mitogenic effect on synovial fibroblasts [5,6,7]. This does not directly suggest DING proteins have an influence on human transcription, these phenotypes are characteristic of an increase in NFκB activity

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Conclusion