# Role of HCV exosomes in intercellular communication

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $407,149

## Abstract

Program Director/Principal Investigator (Hahn, Young S.):
Project Summary:
Chronic HCV infection affects an estimated 3% of the world's population (>180 million people) and is a
worldwide health problem causing end-stage liver diseases including hepatocellular carcinoma (HCC). The
development of HCV-related HCC occurs by advanced fibrosis or cirrhosis. The clinical outcome of HCV
infection and HCC risk depends on a balance between pro- and anti-inflammatory cytokines and the severity of
liver inflammation. Our preliminary data show that exosomes released from HCV-infected hepatocytes contain
the immunoregulatory molecules such as TGF-β. Importantly, HCV exosmes derived from infected hepatocytes
promote intercellular communication with non-parenchymal cells such as Mφ and LSEC. As a result of
receiving signaling from HCV exosomes, Mφ and LSEC are differentiated into fibrotic cells, that activate stellate
cells and induce the development of liver fibrosis. The overall goal of this project is to define the mechanism by
which HCV-derived exosomes from infected hepatocytes drive pro-fibrotic liver microenvironment and explore
potential therapeutic agents to prevent liver fibrosis. In Aim 1, we propose to identify key molecular machinery
required for the secretion of hepatocyte exosomes after HCV infection in in vitro and in vivo. In Aim 2, we will
determine how HCV-derived exosomes induce the activation of fibrotic M2-like Mφ. In Aim 3, we will determine
how HCV-derived exosomes induce fibrotic LSEC differentiation and explore a therapeutic strategy for
preventing fibrosis. The studies proposed here will break new ground for identifying factors crucial for driving
pro-fibrotic liver microenvironment and will help to develop novel therapeutic targets for the prevention of liver
fibrosis.
PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10798128
- **Project number:** 5R01DK122737-05
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Young S. Hahn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $407,149
- **Award type:** 5
- **Project period:** 2020-04-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798128

## Citation

> US National Institutes of Health, RePORTER application 10798128, Role of HCV exosomes in intercellular communication (5R01DK122737-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10798128. Licensed CC0.

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