# Project 5 - HIV-1 Genome Stability & Editing Mediated by Host

> **NIH NIH U54** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $470,242

## Abstract

Project 5: HIV-1 genome stability and editing mediated by host proteins
Summary
In HIV-1 infected cells, many host proteins interact with viral RNA. These interactions can have positive or
negative effects on viral replication. Some of these RNA protein interactions lead to editing of the genome,
while others regulate RNA fate. CRNA investigators have discovered and characterized such several RNA:host
protein interactions that form the basis for Project 5. This project will comprise a mix of structural and biological
approaches to determine the precise nature and role of these important host protein-viral RNA interactions in
HIV-1 replication. In Aim 1 Bieniasz and Smith will determine the X-crystal structure of a novel dinucleotide-
sensing RNA-destabilizing antiviral protein bound to its target. This protein appears to impose a major selective
pressure that drives the biased nucleotide composition of the HIV-1 genome, and likely the genomes of many
other viruses. Its discovery has far reaching implications for the understanding of the selective forces driving
nucleotide composition of viruses and their hosts and the detection of non-self RNA. For Aim 2, APOBEC3
proteins were shown by CRNA investigators to be incorporated into virions through interactions with viral RNA
that appear to mimic the sequence preference of HIV-1 NC. Therefore, Bieniasz, Smith and collaborators will
determine crystal structures of pigtail macaque and human APOBEC3H bound to an RNA target or a DNA
substrate. Finally, Cullen has demonstrated that adenosine methylation at specific sites in the viral genome
facilitates HIV-1 replication, and in Aim 3 of this project Cullen, Rouskin and Telesnitsky will determine the
effect of m6A modification and m6A binding proteins on HIV-1 RNA structure and function, and their role in HIV-
1 replication.

## Key facts

- **NIH application ID:** 9993271
- **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:** $470,242
- **Award type:** 5
- **Project period:** 2012-09-17 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993271

## Citation

> US National Institutes of Health, RePORTER application 9993271, Project 5 - HIV-1 Genome Stability & Editing Mediated by Host (5U54AI150470-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9993271. Licensed CC0.

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