# Human Genetic determinants of HBV recovery

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $800,431

## Abstract

Project Summary
The goal of R01DA013324 renewal is to investigate the host genetic basis for hepatitis B virus (HBV) recovery
in persons living with and without HIV. HBV Infection results in either a successful immune response and
recovery or a chronic infection. Anti-viral drugs control HBV replication but cannot cure chronic hepatitis B
(CHB). Moreover, lifelong therapy is unsustainable for many, which is a major threat to the calls to eliminate
HBV by 2030. A cure for HBV is urgently needed. Understanding how HBV infection is naturally controlled in
many infected persons may provide lessons for how to produce a ‘functional’ cure. There is overwhelming
evidence that host genetic differences explain why some persons can recover from an HBV infection including
family studies, candidate gene studies, and genome wide association studies (GWAS) in Asian populations.
However, these prior GWAS excluded European- and African-ancestry populations despite high HBV
endemicity in Africa (>6% of the population has CHB). We propose to renew R01013324 to fill in the missing
knowledge on host genetic basis for HBV recovery and to extend that work by detailed studies of host and
virus. To this end, Aim 1 focuses on discovering novel genetic variants in a panel of African ancestry
individuals by comparing single nucleotide polymorphisms (SNP) from existing GWAS data in persons with
HBV recovery (N=8667) and with CHB (N=1594). The inclusion of persons living with HIV (PLWH) allows
comparisons of mechanisms of recovery based on HIV. Aim 2 follows by performing a trans-ethnic GWAS
analysis using the African ancestry panel from Aim 1 along with European ancestry individuals from North
America and the UK Biobank and with Chinese ancestry individuals. These GWAS data are available through
collaborators and will also include PLWH. Aim 3 focuses on integrating the host genomic data from Aims 1 and
2 with viral genomics to understand the influence of the host immune response on the viral genome. Deep
sequencing of HBV will be performed on 759 individuals to determine viral amino acid changes that are
associated with host SNPs identified in Aims 1 and 2. A viral-host genomewide interaction analysis will also be
performed, and HBV sequence differences will be compared by HIV status.Our group has made multiple
important discoveries on the host genetic basis of hepatitis C virus spontaneous clearance. Using our
developed expertise, we and our team of international collaborators will apply our methodological approaches
to HBV recovery. Because CHB is the leading cause of liver disease and hepatocellular carcinoma and a
leading cause of morbidity and mortality in PLWH, discovering a functional cure has important public health
implications.

## Key facts

- **NIH application ID:** 10109986
- **Project number:** 5R01AI148049-22
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Priya Duggal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $800,431
- **Award type:** 5
- **Project period:** 1999-09-30 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109986

## Citation

> US National Institutes of Health, RePORTER application 10109986, Human Genetic determinants of HBV recovery (5R01AI148049-22). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10109986. Licensed CC0.

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