title: Gene therapy for human immunodeficiency virus infection in the humanized SCID mouse model.
abstract: BACKGROUND
  The humanized SCID mouse model is an attractive tool for testing gene therapy to combat human immunodeficiency virus infection in vivo.
  
  
  OBJECTIVE
  To devise a more specific gene therapy directed against HIV, replacing the formerly used interferon with either soluble CD4 molecule immunoadhesin (sCD4-IgG) and/or anti-gp41 monoclonal antibody (2F5), or HIV-negative transdominants genes (Tat, Rev).
  
  
  METHODS
  Human monocytoid cell line (U937) was transfected with IFN alpha, beta or gamma genes. 3T3 murine fibroblastic cell line was transfected with sCD4-IgG or 2F5, or both genes, and a human T4 cell line (CEM) was grafted to SCID mice. Negative transdominant genes (Tat, Rev or both) were also transduced in CEM T cell line. Animals were then challenged with HIV-1, Viral load was followed.
  
  
  RESULTS
  IFN alpha or beta were potent anti-HIV, reducing viral load in vivo and inhibiting reverse transcriptase activity in human-removed cells from animals. sCD4-IgG immunoadhesin and gp41 monoclonal antibody resulted in a dramatic reduction of HIV-1 cellular and plasmatic viral load in humanized SCID mice. The simultaneous introduction of negative Tat and Rev genes resulted in a synergistic inhibition of HIV-1 replication in vivo.
  
  
  CONCLUSIONS
  Despite the marked reduction of HIV-1 propagation by IFN genes or by negative Tat and Rev transdominants, the gene therapy using soluble CD4 immunoadhesin or anti-gp41 was a more efficient preventive treatment against HIV infection.
authors.affiliation: Immunology Laboratory for Transplantation and Immunovirology, Edouard Herriot Hospital, Lyon, France. jean-louis.touraine@chu-lyon.fr
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Touraine
authors.forename: Kamel
authors.initials: K
authors.lastname: Sanhadji
authors.forename: Rachel
authors.initials: R
authors.lastname: Sembeil
mesh_terms: D000818:Animals; D016860:CD4 Immunoadhesins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015757:Genes, rev; D015756:Genes, tat; D015316:Genetic Therapy / Q000379:methods*; D015658:HIV Infections / Q000628:therapy*; D006801:Humans; D007372:Interferons / Q000235:genetics* / Q000627:therapeutic use; D051379:Mice; D016513:Mice, SCID; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D014170:Transformation, Genetic / Q000235:genetics
chemical_list: D016860:CD4 Immunoadhesins; D007372:Interferons; D012194:RNA-Directed DNA Polymerase