# Revealing HIV-1 persistence in myeloid cell reservoirs

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $538,346

## Abstract

Abstract.
HIV-1 persistence in ART is maintained predominantly by tissue reservoirs. However, due to challenges in
sampling anatomic sites, particularly in living subjects, most of the information on viral reservoir composition and
dynamics has been gleaned from studies with circulating CD4+ T cells. As a result, the contribution of tissue
resident macrophages to viral persistence, remains elusive. Therefore, there is a need for new approaches that
can reveal the composition and dynamics of anatomic reservoirs in living subjects.
In the previous funding period, we developed new methods capable of interrogating myeloid cell reservoirs in
living subjects. One approach, termed liganded virion immunocapture, gauges the origins of virions in plasma
from their proteomic content. It exploits the fact that the virion membrane is derived from the plasma membrane
and that virions in plasma will therefore contain tags that reflect their host cell origin. With this approach, we
provided evidence that some virions in plasma of individuals undergoing analytic treatment interruption (ATI) had
a myeloid cell origin [1]. In this renewal, we propose to identify some anatomic sources of the myeloid reservoir,
as well as the longevity and dynamics of the myeloid reservoir. Our objectives are to:
Aim 1: Examine the composition of post-ATI viremia to assess the presence of infected myeloid cells,
including CNS microglia, under suppressive ART.
1a: Track the relative frequencies of myeloid-cell-originating virions (liganded virion immunocapture and
macrophage fusogenicity, molecular clock) across an ATI interval to gain insight into the kinetics of myeloid
reservoir reactivation.
1b: Use liganded immunocapture with microglia-specific tags to assess whether microglial-cell-originating virions
populate post-ATI viremia.
Aim 2: Establish the chronicity of the myeloid reservoir, timing of its establishment and its role in evasion
of host cell immunity.
2a: Track the re-emergence of related, myeloid-originating viral variants across sequential ATIs conducted over
a two year period.
2b: Assess T cell epitope escape frequencies in temporally matched (molecular clock), myeloid-derived and
lymphoid-derived virus populations.
2c: Evaluate whether myeloid cell-derived virions populate post-ATI viremia in early ART subjects.
This proposal leverages important and unique clinical cohorts assembled from subjects undergoing single and
sequential ATIs as well acute infection subjects and employs novel methods of examining post-ATI viremia to
gain insight into anatomic myeloid reservoirs that have thus far, remained elusive.

## Key facts

- **NIH application ID:** 10709063
- **Project number:** 2R01MH116701-06
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Mario Stevenson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $538,346
- **Award type:** 2
- **Project period:** 2018-06-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10709063

## Citation

> US National Institutes of Health, RePORTER application 10709063, Revealing HIV-1 persistence in myeloid cell reservoirs (2R01MH116701-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10709063. Licensed CC0.

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