Specific inhibition of human immunodeficiency virus type 1 replication by RNA transcribed in sense and antisense orientation from the 5'-leader/gag region.

The inhibitory effects of expression plasmids on HIV-1 replication were studied in a transient assay system. Test plasmids were co-microinjected with non-defective proviral HIV-1 DNA into a colon-carcinoma cell line (SW480) and the resulting infectious HIV-1 was quantitated after amplification in cocultivated CD4+ MT-4 cells. At a molar ratio of 1:1 and 5:1 plasmids capable of expressing a 410 bp HIV-1 fragment as antisense or sense transcript respectively both specifically inhibited HIV-1 replication up to 70%. This effect was specific for HIV-1 sequences and was not observed upon expression of unrelated RNA-segments. At a molar excess equal to or greater than 15:1, additional inhibitory effects were seen with control plasmids carrying only the strong human cytomegalovirus immediate early (HCMV IE) promoter/enhancer element. The reasons for these findings are discussed.