Research Project
2067582
DESCRIPTION: (Adapted from applicant's abstract) The investigator proposes to identify pharmaceuticals which decrease the frequency of ribosome frameshifting at the HIV gag (specifies virion core proteins)-pol (specifies viral reverse transcriptase) junction. Screening for such agents will be done by developing a plasmid construct in which the expression of a bifunctional hybrid protein is rapidly and quantitatively measured using colorimetric enzyme assays. Expression of the first enzyme in the hybrid will result from a correctly translated product while expression of the second enzyme will result only from a -1 frameshift at the HIV gag-pol ribosome frameshift-inducing sequence. The screening system will be developed in yeast which has recently been shown to respond to the HIV-derived ribosome frameshifting sequence with the same efficiency as is found in a mammalian system. A precise model for the ribosome frameshift required for HIV pol gene expression has been proposed and drugs to be screened will initially be chosen from those already known to effect ribosome functions involved in the HIV sequence-stimulated frameshift.
