Wednesday, April 2, 2025
4/2/2025
Structure of HIV Rev response element - Abstract Human immunodeficiency virus (HIV) targets the immune cells and weakens our defense against many infections and cancer. If not treated, HIV can progress into acquired immunodeficiency syndrome (AIDS). Although antiretroviral therapy is a key component in HIV treatment and prevention, the rapid development of drug-resistant HIV strains limits the selection of effective therapies available for patients. Thus, there is an urgent need to identify alternative viral targets for inhibition. An essential yet poorly understood step in HIV replication is Rev-response element (RRE) mediated nuclear export of the viral RNAs. During HIV infection, partially spliced and unspliced viral RNAs need to be exported from the host cell nucleus to the cytoplasm to synthesize viral proteins and assemble virions. Since incompletely spliced transcripts cannot be exported by the nuclear export system, HIV uses a specific RNA sequence Rev Response Element (RRE) that are present in the incompletely spliced viral RNAs that viral Rev protein specifically recognizes. Multimeric Rev proteins bind to the RRE structure and recruit the nuclear export complex for cytoplasmic translocation of the viral RNAs. However, the architecture of the highly specific RRE-Rev multimeric complex is unknown, largely due to the lack of the RRE structure. We will use RNA-scaffold approaches that we developed and determine the structures of the initial high-affinity Rev binding site of RRE (stem-loop II) and the full-length RRE. We will further characterize the molecular interactions between RRE and Rev. Understanding the contribution of RNA structure that drive Rev oligomerization will aid development of HIV therapeutics that target RRE and Rev interaction.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).