# Structure of HIV Rev response element

> **NIH NIH R21** · TRUSTEES OF INDIANA UNIVERSITY · 2024 · $237,750

## Abstract

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.

## Key facts

- **NIH application ID:** 11009129
- **Project number:** 1R21AI181621-01A1
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Kyung H Choi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $237,750
- **Award type:** 1
- **Project period:** 2024-05-23 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11009129

## Citation

> US National Institutes of Health, RePORTER application 11009129, Structure of HIV Rev response element (1R21AI181621-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/11009129. Licensed CC0.

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