# Characterizing subsets of HIV-infected and uninfected CD14+CD16+ monocytes that contribute to neuropathogenesis

> **NIH NIH F31** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $53,994

## Abstract

ABSTRACT
Approximately 38 million people worldwide are living with HIV. Despite antiretroviral therapy (ART), 15-40% of
people with HIV (PWH) develop HIV-associated neurocognitive impairments (HIV-NCI). HIV enters the brain
early, often before people are aware of their HIV status or diagnosed. One mechanism for CNS infection is the
transmigration of HIV-infected intermediate CD14+CD16+ monocytes across the blood-brain barrier (BBB).
CD14+CD16+, or mature monocytes are increased in the blood of PWH, are the most susceptible to HIV infection,
and preferentially transmigrate across the BBB. This transmigration across the BBB contributes to the
establishment and reseeding of CNS viral reservoirs and chronic neuroinflammation that results in a neurotoxic
environment and neuronal injury that mediates HIV-NCI development. Therefore, characterizing mature
monocytes is critical to understanding the mechanisms by which they contribute to the pathogenesis of
inflammatory diseases in the presence of HIV, and to define ways to block their pathological effects. To
characterize functional properties of mature monocytes and the effects of HIV infection in these cells, we
previously performed single-cell RNA sequencing (scRNA-seq) of uninfected and HIV-infected mature
monocytes. This study showed that both populations separated into 9 monocyte clusters. Expression of genes
from molecular pathways involved in migratory, inflammatory, or neurotoxic functions in each cluster compared
to other clusters revealed two groups of monocyte clusters in both uninfected and HIV-infected cells, with
increased expression of most genes in these pathways in one cluster group (Group 1) compared to the other
(Group 2). Whether this difference in gene expression indicates increased transmigratory, inflammatory, and
neurotoxic properties of monocytes in clusters from Group 1 compared to those from Group 2 is unknown. We
hypothesize that uninfected and HIV-infected mature monocytes in Group 1 clusters express high levels of genes
in migratory and inflammatory functions, they preferentially transmigrate across the BBB to CCL2, and produce
more inflammatory cytokines, chemokines, and ROS that contribute to HIV neuropathogenesis than Group 2
monocyte clusters. Aim 1: Characterize the transcriptome of Group 1 and Group 2 mature monocyte clusters to
identify mechanisms of their contributions to increased inflammation and BBB transmigration. We will validate
that group 1 clusters show increased median fluorescence intensity of proteins that correlate with genes
expressed in Group 1 monocyte clusters by flow cytometry, and confirm expression of these genes by qRT-PCR.
Aim 2: Characterize BBB transmigration and inflammatory properties of Group 1 compared to Group 2 mature
monocyte clusters. We will determine functional properties of Group 1 monocyte clusters by determining ROS,
cytokine, and chemokine production by flow cytometry, transmigration propensity with our in vitro BBB model,
and blo...

## Key facts

- **NIH application ID:** 10778214
- **Project number:** 5F31MH132471-02
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Vanessa Yasmeen Ruiz
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,994
- **Award type:** 5
- **Project period:** 2023-01-16 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10778214

## Citation

> US National Institutes of Health, RePORTER application 10778214, Characterizing subsets of HIV-infected and uninfected CD14+CD16+ monocytes that contribute to neuropathogenesis (5F31MH132471-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10778214. Licensed CC0.

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