Gone therapy for human immunodeficiency virus infection in the humanized SCID mouse model

Background: The humanizaed SCID mouse model is an attractive tool for testing gene therapy to combat human immunodeficiency virus infection in vivo. Objectives: 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 IFNalpha, beta, gamma genes. 3T3 murine fibroblastic cell line was transfected withsCD4-IgG or 2F5, or both genes, and a human T4 cell line (CEM) was grafted to SCID mice. Negative transdominat 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: IFNalpha 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.