# Cell surface receptors promoting hepatitis B virus infection

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $468,834

## Abstract

Chronic hepatitis B virus (HBV) infection remains a major global health problem despite of
effective HBV vaccine, affecting 240 million people worldwide and 1.25 million Americans. HBV
is a leading cause of liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular
carcinoma (HCC). Prophylactic HBV vaccine is effective to prevent new HBV infection but does
not offer therapeutic benefit to the hundreds of million people already infected with HBV. Current
antiviral drugs consisting of interferon and nucleoside analogues are not curative of hepatitis B.
The World Health Organization has called for the elimination of viral hepatitis as a public health
threat by 2030. The biggest challenge for a cure of hepatitis B is how to eliminate HBV covalently
closed circular DNA (cccDNA), which is the molecular basis for persistent viral replication. Thus,
there is an urgent need to discover and develop new classes of more efficacious antiviral drugs
for curing hepatitis B. The lack of robust cell culture and small animal models of HBV propagation
is a major barrier towards finding a cure for hepatitis B. Recently, we have developed a robust
HBV cell culture system. More significantly, we have discovered that human apolipoprotein E
(apoE) is enriched on the HBV envelope and promotes HBV infection and production. Our
preliminary studies also found that the low-density lipoprotein receptor (LDLR) and several core
proteins of heparan sulfate proteoglycans (HSPGs) are important for HBV infection. We
hypothesize that the LDLR family proteins and HSPGs serve as cell surface receptors promoting
HBV infection. Our overall goal is to determine the roles and underlying molecular mechanism
of the LDLR family proteins and HSPGs in HBV infection in vitro and in vivo. This objective will be
addressed by three specific aims: 1) to determine the importance and molecular mechanism of
the LDLR family proteins in HBV infection; 2) to define the role and molecular basis of HSPGs in
HBV infection; and 3) to determine the physiological importance of LDLR in HBV infection in vivo
using humanized mice and a new transgenic HBV mouse model. The successful completion of
this application will fill a knowledge gap about new HBV attachment receptors and provide novel
targets and transgenic HBV mouse model for discovery and development of new therapeutics
towards a cure of chronic hepatitis B.

## Key facts

- **NIH application ID:** 10034949
- **Project number:** 1R01DK125734-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** GUANGXIANG George LUO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $468,834
- **Award type:** 1
- **Project period:** 2020-07-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10034949

## Citation

> US National Institutes of Health, RePORTER application 10034949, Cell surface receptors promoting hepatitis B virus infection (1R01DK125734-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10034949. Licensed CC0.

---

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