Human-Phosphate-Binding-Protein inhibits HIV-1 gene transcription and replication

Thomas Cherrier,Valentin Le Douce,Andrea Janossy,Olivier Rohr,Alicia Jeudy,Ermanno Candolfi,Guillaume Gotthard,Patrick Masson,Christian Schwartz,Houda Hallay,Mikael Elias,Eric Chabrière

doi:10.1186/1743-422x-8-352

Abstract

The Human Phosphate-Binding protein (HPBP) is a serendipitously discovered lipoprotein that binds phosphate with high affinity. HPBP belongs to the DING protein family, involved in various biological processes like cell cycle regulation. We report that HPBP inhibits HIV-1 gene transcription and replication in T cell line, primary peripherical blood lymphocytes and primary macrophages. We show that HPBP is efficient in naïve and HIV-1 AZT-resistant strains. Our results revealed HPBP as a new and potent anti HIV molecule that inhibits transcription of the virus, which has not yet been targeted by HAART and therefore opens new strategies in the treatment of HIV infection.

Highlights

Human immunodeficiency 1 (HIV-1), identified in 1983 [1], remains a global health threat responsible for a world-wide pandemic
Previous observations suggested that p27SJ, another member of the DING protein family isolated from the plant Hypericum perforatum, represses HIV-1 replication and transcription [25,45,46]
P27SJ has a dual role on MCP1(monocyte chemoattractant protein 1) gene transcription being an activator at low concentration and an inhibitor at high concentration [47]

Summary

Introduction

Human immunodeficiency 1 (HIV-1), identified in 1983 [1], remains a global health threat responsible for a world-wide pandemic. AIDS pandemic has stabilized on a global scale in 2008 with an estimated 33 million people infected worldwide (data from UN, 2008). Several problems have been encountered since the introduction of HAART, and improvements in the design of drugs for HIV-1 are needed. HAART has several serious side effects leading to treatment interruption. Another major concern is related to the emergence of multidrug resistant viruses which has been reported in patients receiving HAART [3,4,5]. New antiviral drugs are needed with activities against both wild type and mutant viruses.

Methods

Results

Conclusion