GAG PROTEIN/RNA INTERACTIONS IN THE HIV LIFECYCLE

University Of California San Francisco, San Francisco CA

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Abstract

DESCRIPTION: The investigator proposes to characterize the HIV-1 Gag/y interaction in molecular detail in vitro, and to evaluate its role in the biology of HIV-1 infection. High-resolution footprinting and mutagenesis will be performed to map specific residues and structures in y required for binding of Gag, RNA dimerization, and other in vitro activities. RNA conformational changes induced by Gag binding will be investigated, and the investigator will determine how binding to individual sites promotes or regulates y functions. Mutant HIV-1 proviruses with defined defects in y will be created and tested for their effects on virus infectivity, RNA packaging fidelity, particle morphology, and the efficiency of reverse transcription. Finally, the investigator will test newly-identified heterologous RNA ligands that bind with greater affinity than y to HIV-1 Gag for their ability to replace the native y locus in HIV-1 RNA and to act as competitive trans-inhibitors of y function and virus replication.