# Defining a Role for Liver Myeloid Cells in Viral Persistence under ART

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $510,355

## Abstract

The pursuit of a cure for HIV-1 infection is founded on the hypothesis that reservoirs that support viral persistence
are amenable to elimination. As such, most of the research on HIV-1 cure and remission has centered on
identifying the dynamics of CD4+ T cell reservoirs as well as on approaches to eliminate them. We recently
presented evidence that following analytic treatment interruption (ATI), rebounding viremia comprised virions
that were highly macrophage tropic. Through the use of a novel immunoaffinity enrichment method, we further
demonstrated that macrophage-tropic viruses in post-ATI plasma have a myeloid cell origin [1]. These
observations define myeloid cells as a reservoir under suppressive ART and that these reservoirs require
consideration in the design of viral remission and cure strategies
The myeloid compartments that house HIV-1 reservoirs under ART are unkown. However, the approaches we
developed have the capacity to yield this information. Those approaches hinge upon our demonstration that
virion membranes are derived from the host cell plasma membrane and as such, virions harbor ligands that
inform on their host cell of origin. We will adopt these approaches to address the long-standing issue of whether
Kupffer Cells in the liver, which is the largest myeloid compartment of the immune system, serve as viral
reservoirs in the face of suppressive ART. Our objectives are:
 Aim1: Identify host cell ligands on virions derived from primary Kupffer cells that enable
immunoaffinity isolation of virions with a Kupffer cell origin in post ATI-plasma.
 Aim 2: Derive libraries of full length viral envelopes from liver tissue of HIV-1-infected individuals
and assess their cellular tropism and dynamics by high-throughput viral phenotyping and Molecular
Clock analysis, respectively.
 Aim 3: Employ liganded virion capture and high discrimation Taq (HiDi Taq) polymerase-directed
allele amplification to assess whether virions in tissue-matched plasma originate from Kupffer cells and
whether immunocaptured virions from plasma and proviruses from liver tissue exhibit related virological
characteristics and phylogenetic structures.
 This proposal leverages important clinical resources that will be used to define whether Kupffer cells
serve as viral reservoirs of HIV-1. The information derived from this proposal will provide the rationale for the
identification of tailored approaches to eliminate myeloid reservoirs within the liver and other myeloid
compartments.

## Key facts

- **NIH application ID:** 10654037
- **Project number:** 5R01DK131533-02
- **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:** $510,355
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10654037

## Citation

> US National Institutes of Health, RePORTER application 10654037, Defining a Role for Liver Myeloid Cells in Viral Persistence under ART (5R01DK131533-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10654037. Licensed CC0.

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