# Transcriptional Control of HIV Latency in Hematopoietic Stem and Progenitor Cells

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $38,690

## Abstract

Abstract
HIV establishes a persistent infection despite the host immune response and treatment with
antiretroviral therapy (ART). This is due to the establishment of latent infections in a small subset
of cells – predominantly resting memory T lymphocytes (TRM), which can survive for decades, and
from which virus can rebound with interruption in therapy. In addition to CD4+ T cells, we have
demonstrated that HIV can also infect and establish latent infections in CD4+ hematopoietic stem
and progenitor cells (HSPCs). HSPCs are extremely long-lived, have the potential for self-
renewal, and importantly, contribute to viremia in patients that have maintained ART for many
years. In vitro studies of HIV latency demonstrate immediate latency establishment in HSPCs in
contrast to a period of weeks required for most T cell latency models. Some of the mechanisms
that control latency in CD4+ T cells have been well established and primarily involve epigenetic
factors such as histone methylation or lack of recruitment of an activating factor to the 5’ long
terminal repeat (LTR). Whether silencing of HIV is established similarly in HSPCs has yet to be
determined. Discovering the biochemical factors that control latency reversal as well as markers
that identify latently infected cells could facilitate targeting or activation of latently infected cells
and elimination of the viral reservoir. Our recent work suggests that the global transcriptomic and
epigenetic changes that occur during hematopoietic differentiation affect viral latency and
activation. We have found that latency in the most primitive HSPCs is relatively resistant to
reversal by histone deacetylase inhibitors. Moreover, we generated intriguing preliminary data
suggesting the novel hypothesis that unique stem cell specific mechanisms play important roles
in silencing HIV gene expression in HSPCs. To test this hypothesis, we will use a combination of
single-cell, biochemical, and molecular biology techniques in addition to computational
approaches to better define the characteristics of latently versus actively infected HSPCs with the
following aims: (1) determine the transcriptomic and epigenomic landscape of latent versus
actively infected HSPCs, and (2) determine the extent to which integration site and local chromatin
structure play a role in silencing HIV proviral genomes in HSPCs. Together, these aims will identify
DNA and RNA biomarkers of latency, uncover HSPC specific silencing mechanisms and produce
an integrated transcriptomic and epigenomic atlas of the HIV reservoir in HSPCs.

## Key facts

- **NIH application ID:** 10508513
- **Project number:** 5F31AI155047-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Maria Virgilio
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $38,690
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10508513

## Citation

> US National Institutes of Health, RePORTER application 10508513, Transcriptional Control of HIV Latency in Hematopoietic Stem and Progenitor Cells (5F31AI155047-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10508513. Licensed CC0.

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