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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Huelsmann Peter M, Hofmann Andreas D, Knoepfel Stefanie A, Popp Jasmin, Rauch Pia, Di Giallonardo Francesca, Danke Christina, Gueckel Eva, Schambach Axel, Wolff Horst, Metzner Karin J, Berens Christian,
Project Minority quasispecies of drug-resistant HIV-1: Emergence, transmission, dynamics, and clinical relevance in acute and chronic HIV-1 infection
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Original article (peer-reviewed)

Journal BMC biotechnology
Volume (Issue) 11
Page(s) 4 - 4
Title of proceedings BMC biotechnology
DOI 10.1186/1472-6750-11-4


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.