# RNA Protein interactions in HIV-1 replication

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2021 · $500,288

## Abstract

Project Summary
The HIV-1 RNA genome contains cis-acting RNA sequences elements that control many aspects of viral
replication. In addition, there are remarkable global compositional features of the HIV-1 RNA genome that are
heretofore unexplained. An essential feature of the HIV-1 RNA genome that enables its encapsidation is its
ability to bind to the nucleocapsid (NC) domain in Gag. While a specific interaction between the packaging
sequence at the 5' end of the viral genome and Gag is well known to be important for initiating HIV-1 genome
packaging it is also well known that the packaging sequence is not absolutely required, nor is it sufficient for
highly selective packaging of HIV-1 RNA. In Aim 1 we will determine whether nucleotide composition and
sequence motifs throughout the HIV-1 genome constitute a multipartite packaging signal, and whether this
feature, coupled with the changing RNA binding specificity of Gag/NC can account for the remarkably specific
packaging of HIV-1 genomes into virions. The Matrix (MA) domain of Gag also binds to RNA, as well as to
membranes, via a highly basic surface. However, in the case of MA, ~10 host tRNAs are bound with
exceptional specificity in the cytoplasm of infected cells. These findings lead to the hypothesis, to be explored
in the ensuing funding cycle, that tRNA regulates HIV-1 assembly dynamics or location. Aim 2 is centered on
our recent discovery of an RNA binding protein that causes turnover of RNA molecules based on their
nucleotide composition. The unusual composition of the HIV-1 genome appears, in part, to represent an
evasion strategy to avoid detection by this this protein. We will determine the molecular mechanisms by which
this apparent host defense mechanism functions.

## Key facts

- **NIH application ID:** 10201459
- **Project number:** 5R01AI050111-21
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Paul D. Bieniasz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $500,288
- **Award type:** 5
- **Project period:** 2001-04-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201459

## Citation

> US National Institutes of Health, RePORTER application 10201459, RNA Protein interactions in HIV-1 replication (5R01AI050111-21). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201459. Licensed CC0.

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