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

BMC Biotechnology

Research Article

Axel Schambach¹  Horst Wolff²  Christina Danke³  Christian Berens³  Jasmin Popp³  Eva Gueckel⁴  Pia Rauch⁵  Andreas D Hofmann⁵  Peter M Huelsmann⁵  Stefanie A Knoepfel⁵  Karin J Metzner⁶  Francesca Di Giallonardo⁷ 

[1] Hannover Medical School, Department of Experimental Hematology, Hannover, Germany;Helmholtz Zentrum München, Institute of Virology, Neuherberg, Germany;University of Erlangen-Nuremberg, Department Biology, Erlangen, Germany;University of Erlangen-Nuremberg, Department of Internal Medicine III, Erlangen, Germany;University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, Erlangen, Germany;University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, Erlangen, Germany;University of Zurich, University Hospital Zurich, Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Switzerland;University of Zurich, University Hospital Zurich, Department of Medicine, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Switzerland;

关键词: Suicide Gene;    Suicide Vector;    Suicide Protein;   

DOI  :  10.1186/1472-6750-11-4

 received in 2010-03-09, accepted in 2011-01-11,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundRegulated 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.ResultsWhen 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.ConclusionsThis 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.

【 授权许可】

Unknown   
© Huelsmann et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.