POSITIVE SELECTION SYSTEM TO SCREEN FOR INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS-1 TRANSCRIPTION

We describe a transcription-based assay system to screen for antiviral drugs in vivo, The system consists of two transcription units, a cyto megalovirus promoter driving a reporter gene physically linked to an H IV-1 promoter oriented in the opposite direction. Based on the arrange ment of the transcription units, enhanced HIV-1 promoter activity in t he presence of the viral transactivating Tat protein downregulates rep orter gene expression initiated from the CMV promoter, Inhibitors of H IV-1 transcription relieve the suppression and are identified by an in crease in reporter gene expression. This positive selection system all ows discrimination between drugs that nonspecifically block cellular f unctions by cytotoxicity and molecules that specifically repress HIV-1 promoter activity.