# Virus-host interactions for a cure against HBV

> **NIH NIH R56** · EMORY UNIVERSITY · 2024 · $510,306

## Abstract

Project Summary
Hepatitis B virus (HBV) infections affect the lives of more than 296 million people who are chronically infected
with HBV and are at risk of developing liver cirrhosis and hepatocellular carcinoma. Every year approximately
820,000 people die due to HBV-related complications and currently there is no effective cure. The available
treatments include nucleoside analogs and interferon alpha (IFNα). In the case of IFNα treatment there is a 10%
cure. Even though this number is not satisfactory it proves that HBV cure is possible. The mechanisms by which
IFNα leads to a cure are still not well understood. HBV genotypes and mutations in the pre-core region that result
in HBV e antigen (HBeAg) negative serology, have been associated with different health risks in chronic HBV
and sensitivity to IFNα treatment. Chronicity of HBV infections is linked to the stability and maintenance of the
covalently closed circular DNA (cccDNA), which is the nuclear form of the HBV genome. The goal for a functional
HBV cure relies on strategies that will either eliminate or inactivate the cccDNA. Therapies that are based on
nucleoside analogs do not target the cccDNA while the mechanisms by which IFNα blocks HBV replication are
not entirely understood in respect to the direct or indirect effects on the cccDNA. Several investigational direct
acting antivirals (DAAs) including capsid assembly modulators (CAMs) and antisense oligonucleotides (ASOs)
have emerged as possible components in future combination therapies with the hope that a finite treatment will
be sufficient by activating the immune system and targeting the cccDNA. Host factors are being also investigated
both for understanding the basic biology of HBV but also as possible therapeutic interventions. Our recent
advances in cell culture and animal models that are based on the use of primary human hepatocytes can now
be exploited and combined with multiomics approaches and novel CRISPR validation tools to discover host
restriction and host dependency factors in the context of chronic HBV infection. The impact of HBV genotypes
and mutants provides a great tool to determine differences in chronic HBV and in the context of treatment with
IFNα. Moreover, DAAs that lead to activation of innate immunity may be part of future combination therapies. In
all, these studies combine expertise from multiple fields with the goal of advancing our knowledge in virus-host
interactions and leading to curative therapies against chronic HBV.

## Key facts

- **NIH application ID:** 11136654
- **Project number:** 1R56AI182395-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Eleftherios Michailidis
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $510,306
- **Award type:** 1
- **Project period:** 2024-08-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11136654

## Citation

> US National Institutes of Health, RePORTER application 11136654, Virus-host interactions for a cure against HBV (1R56AI182395-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11136654. Licensed CC0.

---

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