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Open Access Research article

A suicide gene approach using the human pro-apoptotic protein tBid inhibits HIV-1 replication

Peter M Huelsmann1, Andreas D Hofmann1, Stefanie A Knoepfel1, Jasmin Popp2, Pia Rauch1, Francesca Di Giallonardo3, Christina Danke2, Eva Gueckel4, Axel Schambach5, Horst Wolff6, Karin J Metzner13* and Christian Berens2*

Author Affiliations

1 University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, Erlangen, Germany

2 University of Erlangen-Nuremberg, Department Biology, Erlangen, Germany

3 University of Zurich, University Hospital Zurich, Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Switzerland

4 University of Erlangen-Nuremberg, Department of Internal Medicine III, Erlangen, Germany

5 Hannover Medical School, Department of Experimental Hematology, Hannover, Germany

6 Helmholtz Zentrum M√ľnchen, Institute of Virology, Neuherberg, Germany

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BMC Biotechnology 2011, 11:4  doi:10.1186/1472-6750-11-4

Published: 11 January 2011

Abstract

Background

Regulated expression of suicide genes is a powerful tool to eliminate specific subsets of cells and will find widespread usage in both basic and applied science. A promising example is the specific elimination of human immunodeficiency virus type 1 (HIV-1) infected cells by LTR-driven suicide genes. The success of this approach, however, depends on a fast and effective suicide gene, which is expressed exclusively in HIV-1 infected cells. These preconditions have not yet been completely fulfilled and, thus, success of suicide approaches has been limited so far. We tested truncated Bid (tBid), a human pro-apoptotic protein that induces apoptosis very rapidly and efficiently, as suicide gene for gene therapy against HIV-1 infection.

Results

When tBid was introduced into the HIV-1 LTR-based, Tat- and Rev-dependent transgene expression vector pLRed(INS)2R, very efficient induction of apoptosis was observed within 24 hours, but only in the presence of both HIV-1 regulatory proteins Tat and Rev. Induction of apoptosis was not observed in their absence. Cells containing this vector rapidly died when transfected with plasmids containing full-length viral genomic DNA, completely eliminating the chance for HIV-1 replication. Viral replication was also strongly reduced when cells were infected with HIV-1 particles.

Conclusions

This suicide vector has the potential to establish a safe and effective gene therapy approach to exclusively eliminate HIV-1 infected cells before infectious virus particles are released.