# Collaborative Integration of Hepatitis B Molecular Virology and Mathematical/Computational Modeling

> **NIH NIH R01** · LOYOLA UNIVERSITY CHICAGO · 2020 · $450,911

## Abstract

Despite an effective vaccine, hepatitis B virus (HBV) continues to impose an enormous global
health burden. Over 260 million are HBV infected worldwide, causing chronic hepatitis and more
than 400,000 death per year due to hepatocellular carcinoma. While currently available drugs can
suppress HBV replication only a small subset of patients are cured. As such, a deeper
understanding of HBV infection dynamics at the molecular level is needed to enable the
development of more effective (i.e. curative) therapeutics. Fortunately, significant advances have
been made recently with the establishment of chimeric mouse models with humanized livers that
retain permissiveness to HBV infection and the identification of sodium taurocholate
cotransporting polypeptide (NTCP) as the HBV entry receptor which when expressed
exogenously renders hepatoma cell cultures permissive to HBV infection in vitro. Hence, for the
first time, we can perform HBV infections in mice and cell culture to characterizing HBV lifecycle
and treatment response. Towards this end, the objective of this cross disciplinary R01 is to
increase our knowledge of HBV by formulating and testing mathematical/computational models
of HBV infection. The premise is that a more quantitative understanding of HBV infection and
treatment dynamics will help define rate limiting steps, identify more effective antiviral targets and
predict mechanism of action (MOA) of current drugs and those under development thus facilitating
the design of improved therapeutics. The uniquely close collaborative effort among experienced
virologists and expert viral dynamic and computational scientists proposed is critical for facilitating
the development and utilization of data-driven modeling concepts to elucidate the detailed
molecular biological processes that regulate HBV. Specifically, we propose to (i) Quantify HBV
infection kinetics in uPA-SCID chimeric mice with humanized livers and develop
mathematical/computational models to elucidate the processes that regulate HBV dynamics, (ii)
Refine our understanding of HBV infection at the molecular level by characterizing HBV infection
kinetics in vitro and developing multi-compartmental mathematical/computational models to
elucidate the processes that regulate HBV dynamics, (iii) Validate and refine our understanding
of HBV infection by characterizing/ modeling HBV treatment response to antivirals of known
mechanism of action, and (iv) Use HBV mathematical/computational models to predict the MOA
by which clinically relevant drugs inhibit HBV and empirically test those hypotheses.

## Key facts

- **NIH application ID:** 9850513
- **Project number:** 5R01AI144112-02
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Harel Dahari
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,911
- **Award type:** 5
- **Project period:** 2019-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850513

## Citation

> US National Institutes of Health, RePORTER application 9850513, Collaborative Integration of Hepatitis B Molecular Virology and Mathematical/Computational Modeling (5R01AI144112-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9850513. Licensed CC0.

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