# Identification of Host and Viral Determinants of Human Norovirus B cell Infection

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $477,833

## Abstract

SUMMARY
Human noroviruses are a leading global cause of severe childhood diarrhea and gastroenteritis outbreaks.
However, development of therapeutic and preventative strategies has been severely limited by the inability to
propagate these viruses in culture. We recently discovered that noroviruses infect B cells in vitro and in vivo,
and that they utilize commensal bacteria as a co-factor for infection. These novel findings led directly to our
development of the first human norovirus cultivation system, a tool that will revolutionize norovirus research.
We are now uniquely poised to identify host restriction and susceptibility factors influencing human
norovirus infection of B cells as well as viral determinants of B cell infection. We hypothesize that this
information will reveal key virus-host interactions that can guide the development of novel therapeutics,
vaccine candidates, and enhanced diagnostic strategies. In Specific Aim 1, we will utilize complementary
targeted and unbiased approaches to develop a comprehensive set of host factors that either restrict or
promote human norovirus infection of B cells. In Specific Aim 2, a multi-pronged approach will be undertaken
to identify viral determinants of in vitro replicative fitness. Strategies include serial passaging of virus in
permissive cells and testing a diverse set of human norovirus genotypes for B cell infectivity. We will also
construct a human norovirus reverse genetics system to test adaptive mutations for phenotypic effects. These
studies will not only provide critical insight into host and viral determinants of B cell infection by human
noroviruses but they should also culminate in the development of 2nd generation culture systems supporting
robust infection of a broad panel of viral genotypes.

## Key facts

- **NIH application ID:** 10062847
- **Project number:** 5R01AI123144-05
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Stephanie M Karst
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $477,833
- **Award type:** 5
- **Project period:** 2016-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062847

## Citation

> US National Institutes of Health, RePORTER application 10062847, Identification of Host and Viral Determinants of Human Norovirus B cell Infection (5R01AI123144-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10062847. Licensed CC0.

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