Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-55548
Huelsmann, P M; Hofmann, A D; Knoepfel, S A; Popp, J; Rauch, P; Di Giallonardo, F; Danke, C; Gueckel, E; Schambach, A; Wolff, H; Metzner, K J; Berens, C (2011). A suicide gene approach using the human pro-apoptotic protein tBid inhibits HIV-1 replication. BMC Biotechnology, 11:4.
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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.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases|
|Dewey Decimal Classification:||610 Medicine & health|
|Deposited On:||21 Jan 2012 19:42|
|Last Modified:||16 Dec 2013 14:29|
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