# HIV-1-induced upregulation of m6A modifications of cellular RNA in CD4+ T-cells

> **NIH NIH R21** · UNIVERSITY OF IOWA · 2022 · $193,125

## Abstract

Project Summary/Abstract
This R21 application is in response to PA-19-237: Novel RNAs in Virology (including HIV) and Immune
Regulation: Basic Science and Therapeutic Discovery. In this new project, we propose to investigate the function
and mechanisms of HIV-1-induced upregulation of N6-methyladenosine (m6A) modifications of cellular RNA in
primary CD4+ T cells. Through interdisciplinary collaborations and technical innovations, our team is uniquely
poised to address key questions highlighted in this funding opportunity.
We have investigated the mechanisms by which m6A modifications regulate HIV-1 infection of primary CD4+ T
cells. Interestingly, we found that the HIV-1 envelope protein gp120 upregulates m6A levels of cellular RNA
independently of viral replication in primary CD4+ T cells. Our further study suggested that the interaction
between gp120 and the CD4 receptor is important for HIV-1-induced m6A upregulation of cellular RNA in CD4+
T cells. However, the functional significance and the molecular mechanisms of HIV-1 gp120-induced
upregulation of m6A modifications of cellular RNA in CD4+ T cells remain unknown. We aim to fill these significant
knowledge gaps through the proposed studies that are also aligned well with the goal of the funding opportunity.
We hypothesize that HIV-1 gp120-mediated upregulation of m6A modifications of cellular RNA in primary CD4+
T cells enhances viral replication by altering the epitranscriptomic m6A profile and cellular gene expression. We
designed two specific aims to test the central hypothesis: Aim 1. Epitranscriptomic and transcriptomic analyses
of HIV-1-infected or gp120-treated CD4+ T cells; and Aim 2. Investigate the mechanisms of gp120-induced m6A
upregulation and the effects on primary CD4+ T cell activation and HIV-1 replication.
Overall impact. Defining m6A epitranscriptomic and general transcriptomic profiles of CD4+ T cells will reveal
cellular RNAs involved in regulating HIV-1 infection. Our exploratory studies can identify novel host factors that
are critical for modulating HIV-1 replication and persistence. The expected results will help define the functional
significance of HIV-1 gp120-induced upregulation of cellular RNA m6A levels in primary CD4+ T cells, which will
provide new insights into the molecular mechanisms of HIV-1 persistence in CD4+ T cells.

## Key facts

- **NIH application ID:** 10545493
- **Project number:** 1R21AI170070-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Stacia L Phillips
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $193,125
- **Award type:** 1
- **Project period:** 2022-07-19 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10545493

## Citation

> US National Institutes of Health, RePORTER application 10545493, HIV-1-induced upregulation of m6A modifications of cellular RNA in CD4+ T-cells (1R21AI170070-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10545493. Licensed CC0.

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