An inducible human immunodeficiency virus type 1 (HIV-1) vector which effectively suppresses HIV-1 replication

Recently, gene therapy vectors based upon the human immunodeficiency virus type 1 (HIV-1) genome have been developed. Here, we create an HIV-1 vector which is defective for all HIV-1 genes, but which maintains cis-acting elem ents required for efficient packaging, infection, and expression. In T cell s transduced by this vector, vector expression is low but efficiently induc ed following HIV-1 infection. Remarkably, although the HIV-1 vector does no t contain specific anti-HIV-1 therapeutic genes, the presence of the vector alone is sufficient to inhibit the spread of HIV-1 infection. The mechanis m of inhibition is likely to be at the level of competition for limiting su bstrates required for either efficient packaging or reverse transcription, thereby selecting against propagation of wild-type HIV-1. These results pro vide proof of a concept for potential application of a novel HIV-1 vector i n HIV-1 disease.