# Nef in impaired efferocytosis: a novel mechanism for vascular disease in HIV

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $771,902

## Abstract

Project Summary
Anti-retroviral therapy (ART) has protected many HIV patients against the development of AIDS. HIV
infection has become a treatable disease. Increased risk for atherosclerotic vascular diseases in long-term
HIV survivors or people living with HIV (PLWH) with no detectable virus load, however, is projected to
become a global health burden. Despite its clinical impact, underlying mechanisms for accelerated
atherogenesis in PLWH remain obscure. Macrophages promote the formation of high-risk plaques prone to
vascular events (e.g., macrophage-rich, large necrotic core, think fibrous cap). Macrophages are
heterogeneous and the imbalance of their subpopulations may accelerate atherogenesis. Evidence
suggests that extracellular vesicles (EVs) that contain the HIV-associated protein Nef (Nef EVs) promote
chronic inflammation. We will examine the effects of Nef EVs in the heterogeneity and functions of
macrophages and the formation of atherogenesis.
 Our study represents a dynamic interplay of biology and data science to identify novel mechanisms
and therapeutic targets. We will use a systems approach to test the central hypothesis that Nef EVs
modulate macrophage heterogeneity, shifting the balance toward an atherogenic or less atheroprotective
phenotype. Our preliminary data have led us to the specific biological hypothesis that Nef EVs impair
efferocytosis and contribute to the formation of high-risk atherosclerotic plaques that we will test in three
Specific Aims. In Specific Aim 1, we will conduct a systems-based macrophage profiling, involving unbiased
multi-omics, data integration, and network analysis to identify novel mechanisms for macrophage activation
by Nef EVs. Pilot multi-omics data suggested that Nef EVs suppresses efferocytosis. In Specific Aim 2, we
will validate omics data in vitro and in vivo and address underlying mechanisms for impaired macrophage
efferocytosis by Nef EVs.

## Key facts

- **NIH application ID:** 10904071
- **Project number:** 1R01HL174066-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Elena Aikawa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $771,902
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904071

## Citation

> US National Institutes of Health, RePORTER application 10904071, Nef in impaired efferocytosis: a novel mechanism for vascular disease in HIV (1R01HL174066-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10904071. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*