title: A suicide gene approach using the human pro-apoptotic protein tBid inhibits HIV-1 replication.
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.
authors.affiliation: University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, Erlangen, Germany.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Huelsmann
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Hofmann
authors.forename: Stefanie A
authors.initials: SA
authors.lastname: Knoepfel
authors.forename: Jasmin
authors.initials: J
authors.lastname: Popp
authors.forename: Pia
authors.initials: P
authors.lastname: Rauch
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Giallonardo
authors.forename: Christina
authors.initials: C
authors.lastname: Danke
authors.forename: Eva
authors.initials: E
authors.lastname: Gueckel
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.forename: Horst
authors.initials: H
authors.lastname: Wolff
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Metzner
authors.forename: Christian
authors.initials: C
authors.lastname: Berens
mesh_terms: D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics*; D003001:Cloning, Molecular; D005434:Flow Cytometry; D041722:Genes, Transgenic, Suicide; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D014779:Virus Replication / Q000235:genetics*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D054321:rev Gene Products, Human Immunodeficiency Virus; C514860:rev protein, Human Immunodeficiency Virus-1; D054322:tat Gene Products, Human Immunodeficiency Virus