Expression of the human immunodeficiency virus type 1 primer binding sequence inhibits HIV-1 replication

Optimal targets for anti-human immunodeficiency virus (HIV) moieties are those regions of the viral genome that are greatly conserved. The primer binding site (PBS) of HIV is an 18-nucleotide sequence complementary to the 3' end of tRNA(Lys3) that serves as the primer for HIV-1 reverse transcription. All HIV-1 isolates analyzed to date contain a PBS complementary to tRNA(Lys3) illustrating the conservation of this sequence. We investigated the activity of a hammerhead ribozyme targeting the PBS of HIV-1. CEMss cells transduced with retroviral vectors containing either the PBS hammerhead ribozyme or its complementary sequence (as a control) in the R region of the vector long terminal repeat (LTR) were challenged with HIV-1NL4-3. Surprisingly >80% inhibition of HIV-1 production was observed with the vector containing the (control) sequence complementary to the PBS ribozyme. We propose that the LTR-driven vector transcript containing 18 nucleotides identical to the HIV-1 PBS may act like an RNA decoy to titrate viral proteins such as reverse transcriptase and nucleocapsid away from genuine viral transcripts, thus compromising virus replication.