# Regulation of Norovirus Gene Expression & Replication

> **NIH NIH P01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $485,845

## Abstract

PROJECT SUMMARY: Project 2
The focus of Project 2 of this Program Project is to achieve a fully permissive replication system and detailed
molecular understanding of host and viral functions that control human norovirus (HuNoV) replication. For
almost 50 years, the most significant barrier to HuNoV research was the lack of an efficient in vitro cell
cultivation system. We recently succeeded in establishing a robust and reproducible cultivation system for
many HuNoV strains in human stem cell-derived intestinal enteroids (HIEs) that overcomes the longstanding
hurdle to cultivation. Strain-specific differences in replication were discovered and the system is being used to
study virus neutralization, antiviral activity and HuNoV biology. The goal of Project 2 is to continue to
understand and overcome newly recognized remaining barriers in the cultivation of all HuNoVs in HIEs. We
will address this goal through two aims that outline studies to (i) continue to improve and simplify the
cultivation system by understanding virus entry into cells and (ii) identify the cellular receptor(s) for HuNoVs
(Aim 1), and (iii) understand the molecular mechanisms by which norovirus replication induces and regulates
cellular innate responses and how these cellular responses restrict viral replication and spread (Aim 2).
Therapeutics and host molecules associated with disease and virus clearance (Project 1), and structural
insight into viral-host interactions (Project 3) will be tested for their effects on HuNoV replication. Overall,
these studies are designed to lead to a fully permissive, simple and affordable replication system, gain new
molecular understanding of host and viral functions that control virus replication and provide new insight about
HuNoV biology. The program project brings together a highly collaborative group of investigators with diverse
skills and talents, and substantial record of working together. As in the previous funding period, the
interactions among each project and each of the cores will be extensive such that the activities of each project
will be enhanced considerably over what could be accomplished if the projects were pursued independently.

## Key facts

- **NIH application ID:** 9937154
- **Project number:** 2P01AI057788-16
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Mary Kolb Estes
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $485,845
- **Award type:** 2
- **Project period:** 2003-12-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937154

## Citation

> US National Institutes of Health, RePORTER application 9937154, Regulation of Norovirus Gene Expression & Replication (2P01AI057788-16). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9937154. Licensed CC0.

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