The development and testing of retroviral vectors expressing trans-dominant mutants of HIV-1 proteins to confer anti-HIV-1 resistance.

Trans-dominant mutants of human immunodeficiency virus type 1 (HIV-1) Tat and Rev are attractive candidates for use in gene therapy in the treatment of HIV-1 infections because both are essential for viral replication. Retroviral vectors were constructed to allow either Tat-inducible or Tat- and Rev-inducible expression of trans-dominant mutants of Tat and Rev. These vectors were used to infect a human CD4+ lymphocyte-derived cell line, MT4. To determine the efficacy of various Tat and Rev mutants in inhibiting HIV-1 multiplication, MT4 cells containing mutant-expressing constructs were infected with HIV-1, and the amount of HIV-1 released in the culture medium was measured for up to 30 days. A high level of resistance was observed in cells expressing the double tat/rev mutant in a Tat-inducible manner.