# Hepatitis C virus and autophagic response

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $371,250

## Abstract

PROJECT SUMMARY
 Hepatitis C virus (HCV) is an important human pathogen that can cause severe liver diseases including
acute and chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Studies in recent years indicated
that HCV could induce autophagy both in vitro and in vivo to enhance its replication. As autophagy plays
an important role in maintaining cellular homeostasis, the prolonged perturbation of this pathway by HCV
during chronic infection can have profound consequences on the progression of liver diseases in HCV-
infected patients. Although significant progresses have been made during the past few years to understand
the relationship between HCV and autophagy, many questions remain unanswered. The goal of this
research is to continue our previous studies to further understand the relationship between HCV and
autophagy. In Aim 1, we will continue our previous studies to investigate the biogenesis pathway of
autophagosomes in HCV-infected cells by identifying the origin of these membrane vesicles and determine
whether they are derived from the homotypic fusion of phagophores. As our recent studies indicated that
HCV induced autophagy via a non-canonical pathway, in Aim 2, we will continue to delineate this pathway
and examine the roles of HCV nonstructural proteins in the induction of this pathway. In addition, as our
preliminary studies revealed the specific association of lipid rafts with autophagosomes induced by HCV,
we will also investigate how lipid rafts are recruited to HCV-induced autophagosomes and their possible
role in mediating HCV RNA replication on autophagosomal membranes. We have recently developed a
novel approach to purify autophagosomes from HCV-infected cells for the identification of their associated
protein factors. In Aim 3, we will continue to characterize these protein factors, which include annexin A2,
apolipoprotein E and syntaxin 7, and determine their possible roles in the biogenesis of autophagosomes
and HCV replication. Our proposed research will provide important information for understanding the
interaction between HCV and its host cells and lead to a better understanding of the HCV life cycle and its
pathogenesis. It will also provide important information for understanding the cellular autophagic pathway,
which is frequently exploited by viruses to enhance their replication.

## Key facts

- **NIH application ID:** 9891047
- **Project number:** 5R01DK094652-09
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** J.-H. James Ou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,250
- **Award type:** 5
- **Project period:** 2011-09-21 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891047

## Citation

> US National Institutes of Health, RePORTER application 9891047, Hepatitis C virus and autophagic response (5R01DK094652-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9891047. Licensed CC0.

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