Dose-response resistance to HIV-1/MuLV pseudotype virus ex vivo in a hairpin ribozyme transgenic mouse model

We have investigated the efficacy of a hairpin ribozyme targeting the 5' le ader sequence of HIV-1 RNA in a transgenic model system. Primary spleen cel ls derived from transgenic or control mice were infected with HIV-1/MuLV ps eudotype virus. A significantly reduced susceptibility to infection in ribo zyme-expressing transgenic spleen cells (P = 0.01) was shown. Variation of transgene-expression levels between littermates revealed a dose response be tween ribozyme expression and viral resistance, with an estimated cut off V alue below 0.2 copies of hairpin ribozyme per cell, These findings open up possibilities for studies on ribozyme efficacy and anti-HIV-1 gene therapy.