# Potential Role of Extracellular Vesicles for the Development of HIV Comorbidities

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $647,413

## Abstract

Project Summary
HIV-infected people whose viral load is below target levels due to effective anti-retroviral therapy (ART)
continue to be at increased risk for cardio-pulmonary disease with over 75% of patients with chronic HIV
disease showing clinical manifestations. Recent studies in the laboratories of the applicants provided evidence
that HIV proteins and in particular HIV-Nef is retained in plasma and lung fluids of HIV patients on effective
combined anti-retroviral therapy (ART). Based on this previous work we plan to elucidate in preclinical in vitro
and in vivo models the mechanism of endothelia damage and premature aging. Our main hypothesis is that
intracellular HIV proteins are released from cells together with HIV-Nef and travel through extracellular vesicles
(EV) to cause cardiopulmonary changes leading to comorbidities. In aim 1 we will study HIV-proteins in
extracellular vesicles and their association with specific cargo with focus on surface- and intra-vesicular
orientation. The detection of surface markers for specific EV-associated HIV proteins, will allow for future
therapeutic and diagnostic applications including antibody-based targeting techniques. In aim 2, we will
analyze the role EV-associated HIV proteins in delivering HIV-EV-associated cargo throughout the body to
increase inflammation and cell senescence. Specifically, we will use multi-antibody panels to determine cell
identity and location of the “homed” EV. In aim 3, we will focus on the pathology of the delivered HIV-EV
associated cargo. As a proof of principal we will test specific intervention strategies including ADAM17
inhibitors and senolytic agents in preclinical mouse models for HIV-protein delivery through EV.

## Key facts

- **NIH application ID:** 10082718
- **Project number:** 1R01HL154859-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Matthias Clauss
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $647,413
- **Award type:** 1
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10082718

## Citation

> US National Institutes of Health, RePORTER application 10082718, Potential Role of Extracellular Vesicles for the Development of HIV Comorbidities (1R01HL154859-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10082718. Licensed CC0.

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