# Project 4 - RNA interactions during HIV-1 assembly and maturation

> **NIH NIH U54** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $628,744

## Abstract

Summary
While the Gag-5' leader interaction is crucial for the incorporation of HIV-1 genomes into virions, it is by no
means the only RNA protein interaction that is required for the formation of morphologically accurate, infectious
virions. Indeed, CRNA investigators have discovered non-canonical interactions between HIV-1 proteins
(matrix, integrase, protease) and RNA molecules of host and/or viral origin that are, or may be, crucial for
regulating the timing and location of key events in the formation of infectious virions. Additionally, CRNA
investigators have made key advances in determining the structure of an RNA:RNA interaction (tRNA:U5-PBS)
that is also initiated during virion morphogenesis and is similarly crucial for the generation of infectious virions.
Project 4 will consist of a mixture of structural and functional experiments that will aim to elucidate the
molecular details of these events and their importance during HIV-1 virion genesis. In Aim 1 Summers, Zhang
and Bieniasz will determine the structures of matrix:tRNA complexes that appear to regulate Gag:membrane
binding, in Aim 2 D’Souza, Smith, and Chiu will determine structures and functions of tRNA:U5-PBS:reverse
transcriptase complexes that are formed during virion maturation, but are crucial for initiating subsequent
reverse transcription. In Aim 3, Kutluay and Smith will determine the structure of IN:RNA complexes that
appear crucial for the correct positioning of the ribonucleoprotein complex within the capsid core of mature
virions, and will determine the feasibility of inhibiting this interaction with small molecules. Finally, in Aim 4
Swanstrom and Bieniasz will determine whether RNA:protease interactions that activate protease in vitro also
occur in virions, as well as their functional significance, with a view to eventually determining the structural
features of this interaction.

## Key facts

- **NIH application ID:** 9993270
- **Project number:** 5U54AI150470-09
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Paul D. Bieniasz
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $628,744
- **Award type:** 5
- **Project period:** 2012-09-17 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993270

## Citation

> US National Institutes of Health, RePORTER application 9993270, Project 4 - RNA interactions during HIV-1 assembly and maturation (5U54AI150470-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9993270. Licensed CC0.

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