# Role of Human Apolipoprotein E in Hepatitis B Virus Infection andMorphogenesis

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $438,751

## Abstract

Summary
Hepatitis B virus (HBV) is a common cause of human liver diseases, including chronic hepatitis, steatosis,
fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HBV chronically infects more than 250 million people
worldwide, including 1.25 million in the United States. Although HBV vaccine has greatly contributed to the
reduction of new cases of HBV infection and HCC, it does not offer therapeutic benefits to the hundreds of
millions of chronic HBV carriers. The World Health Organization has called for the elimination of viral hepatitis as
a public health threat by the year 2030. The biggest challenge to curing chronic hepatitis B is the elimination of
HBV covalently closed circular DNA (cccDNA), which is the molecular basis for persistent HBV replication.
Existing antiviral therapies with interferon and/or nucleoside analogs can effectively suppress HBV replication
but do not significantly affect the level of HBV cccDNA. Thus, there is an urgent need to discover and develop
new classes of antiviral drugs capable of eliminating chronic HBV infection. In this regard, a more thorough
understanding of HBV infection, replication, and morphogenesis holds a great promise to identify novel targets
for antiviral drug discovery and development. Through preliminary studies, we have discovered that human
apolipoprotein E (apoE) is associated with infectious HBV. More importantly, our preliminary data suggest that
apoE plays critical roles in both HBV infection and morphogenesis. ApoE-specific antibodies could efficiently
neutralize HBV infectivity. Also, knockdown of apoE expression or knockout of apoE gene resulted in a
remarkable reduction of HBV infection and production. Based on these novel findings, we hypothesize that
apoE is incorporated into HBV virions and plays important roles in HBV infection and morphogenesis in vivo. The
overall goal of this application is to determine the role and underlying molecular mechanisms of apoE in the
promotion of HBV infection and morphogenesis in cell culture and in vivo. Our specific aims are: 1) to determine
the importance of apoE in the infection and morphogenesis of clinical HBV isolates; 2) to determine apoE-binding
receptors and apoE-receptor interactions important for efficient HBV infection; and 3) to illustrate the underlying
molecular mechanism of apoE-mediated promotion of HBV morphogenesis. The successful completion of this
application will result in a paradigm change regarding the roles of cellular proteins in HBV infection and
morphogenesis. The outcomes of our studies will also provide novel molecular targets for discovery and
development of antiviral drugs towards the ultimate elimination of HBV infection.

## Key facts

- **NIH application ID:** 11059365
- **Project number:** 7R01AI151007-05
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** GUANGXIANG George LUO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $438,751
- **Award type:** 7
- **Project period:** 2020-09-22 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11059365

## Citation

> US National Institutes of Health, RePORTER application 11059365, Role of Human Apolipoprotein E in Hepatitis B Virus Infection andMorphogenesis (7R01AI151007-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11059365. Licensed CC0.

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