# Analysis of immunity, viral adaptation and pathogenesis in a new mouse model of HCV-related rodent hepacivirus infection

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2021 · $554,390

## Abstract

Project summary
Many liver pathogens, like hepatitis C virus (HCV), have established mechanisms to subvert the host immune
response and to establish persistent infection. Dissecting these mechanisms and gaining insight into factors
that contribute to viral clearance versus chronicity in the liver is notoriously difficult. Access to human liver
tissue is limited. The only immunocompetent animal model of HCV infection, the chimpanzee, is no longer
readily available for research. However, we have recently succeeded in establishing the first immune-
competent mouse model of an HCV-related virus, Norway rat hepacivirus (NrHV). Our preliminary
characterization of this model revealed significant virological and immunological similarities with HCV infection
in humans. This advance now opens the opportunity to interrogate hepatic antiviral immunity, host-virus
interactions, viral adaptation, immune evasion strategies and pathogenesis of a hepatotropic virus at an
unprecedented level. In this proposal we plan to comprehensively analyze innate and adaptive intrahepatic
immune responses during hepacivirus infection in vivo and to define determinants of viral clearance. The
natural host of NrHV is the rat. In immune-competent mice NrHV is cleared after several weeks of infection.
Thus we plan to adapt this virus to the mouse, select for viral variants that can establish chronicity and
systematically analyze mechanisms of host-adaptation and immune evasion. Through NrHV infection of the
genetically diverse Collaborative Cross mouse colony at UNC, we will map the host genetic determinants of
clearance and persistence. We anticipate that combined approaches of viral adaptation to the murine host and
a host genetic screen will meet an important unmet need in establishing a robust model of virus-associated
liver disease. Taken together, our proposed research will use a diverse and multidisciplinary approach to shed
new light on hepatotropic virus infection in vivo. These insights should provide new strategies for vaccine
development or treatment of virus-associated liver disease.

## Key facts

- **NIH application ID:** 10101611
- **Project number:** 5R01AI131688-05
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Charles M Rice
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $554,390
- **Award type:** 5
- **Project period:** 2017-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101611

## Citation

> US National Institutes of Health, RePORTER application 10101611, Analysis of immunity, viral adaptation and pathogenesis in a new mouse model of HCV-related rodent hepacivirus infection (5R01AI131688-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10101611. Licensed CC0.

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