a suicide gene approach using the human pro-apoptotic protein tbid inhibits hiv-1 replication自杀基因的方法使用人类pro-apoptotic蛋白质tbid抑制hiv - 1复制.pdfVIP

Huelsmann et al. BMC Biotechnology 2011, 11:4 /1472-6750/11/4 RESEARCH ARTICLE Open Access A suicide gene approach using the human pro- apoptotic protein tBid inhibits HIV-1 replication 1† 1† 1 2 1 Peter M Huelsmann , Andreas D Hofmann , Stefanie A Knoepfel , Jasmin Popp , Pia Rauch , 3 2 4 5 6 1,3* Francesca Di Giallonardo , Christina Danke , Eva Gueckel , Axel Schambach , Horst Wolff , Karin J Metzner , Christian Berens2* 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 transfe