# Mechanisms of parvovirus replication in viral hepatitis

> **NIH NIH K08** · CORNELL UNIVERSITY · 2022 · $217,225

## Abstract

Project Summary
 The study of animal viruses has been critical for understanding basic disease mechanisms, including the
pathogenesis of related human viruses. This Mentored Clinical Scientist Research Career Development Award
proposal presents a five-year research program to study the mechanisms by which a novel parvovirus
successfully replicates in terminally differentiated hepatocytes. Equine parvovirus-Hepatitis (EqPV-H), a novel
Copiparvovirus, is known to cause hepatitis and fulminant hepatic necrosis in horses. Preliminary data
demonstrate multiple similarities between EqPV-H in horses and parvovirus B19 in humans, including high
prevalence in clinically healthy individuals and rare but important associations with fulminant hepatitis.
Parvoviruses utilize either the host cell replication machinery or the DNA damage response (DDR) pathway to
replicate their viral genomes. The foundation for this proposal is based on studies evaluating the cellular division
status of hepatocytes infected with EqPV-H following experimental inoculation in vivo that suggest that cells with
viral replication are most commonly in G0 phase of the cell cycle.
 This proposal will address the following specific aims: Aim 1) Determine the cellular division and DNA
damage response (DDR) status of EqPV-H-infected hepatocytes and association with pathology in situ; Aim 2)
Evaluate the impact of DNA damage-induced DDR activation and DDR inhibition on EqPV-H replication and
hepatotoxicity in vitro; and Aim 3) Determine the role of host cell polymerases in EqPV-H replication in vitro.
These aims align with Dr. Jager’s career development goals: 1) Training in cell culture development and
optimization; 2) Training in molecular virology, cell biology, and toxicology; and 3) Training in confocal
microscopy and spatial transcriptomics. To achieve these goals, Dr. Jager has assembled a highly qualified team
of mentors including: his primary mentor, Dr. Gerlinde Van de Walle, a veterinary clinician-basic scientist with
expertise in viral pathogenesis and development of novel cell culture systems; co-mentor Dr. Colin Parrish, a
skilled molecular virologist with extensive parvovirus research experience; and co-mentor Dr. Robert Weiss with
expertise in the DDR pathway. Additionally, the team includes collaborators with expertise in parvoviral
replication dynamics, hepatopathology, and equine parvovirus.
 The candidate plans to submit grants for further federal funding, including an R21 or R01 in the fourth
year, with the goal of achieving independence. This K08 award will allow Dr. Jager to develop a sub-specialty in
hepatopathology and viral pathogenesis that will help launch his academic career as an independent clinician-
scientist.

## Key facts

- **NIH application ID:** 10525014
- **Project number:** 1K08AI163401-01A1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Mason Cameron Jager
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $217,225
- **Award type:** 1
- **Project period:** 2022-08-12 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525014

## Citation

> US National Institutes of Health, RePORTER application 10525014, Mechanisms of parvovirus replication in viral hepatitis (1K08AI163401-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10525014. Licensed CC0.

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