# Determinants of Enteric Calicivirus Infection.

> **NIH NIH R01** · TEXAS A&M AGRILIFE RESEARCH · 2024 · $373,214

## Abstract

PROJECT SUMMARY
Human norovirus (HuNoV) gastroenteritis is a significant public health burden worldwide. The lack of a robust
and reproducible HuNoV cell culture system still limits our ability to study fundamental aspects of HuNoV
infection. While several recent breakthroughs increased our ability to propagate HuNoVs in vitro (e.g. B cell
and human enteroid cultures), these systems are not robust enough, can be time consuming and expensive or
hard to replicate. The surrogate models available for HuNoV research do not necessarily reflect essential
biological features of HuNoVs and their natural host. In this proposal we will use our novel rhesus enteric
caliciviruses (ReCV) model that reflects the biological features and diversity of HuNoVs to identify host
determinants of infection. Zoonotic/interspecies transmission of ReCVs and HuNoVs between human and non-
human primate hosts suggests evolutionary conservation of shared factors of host susceptibility between the
two genera. Here we seek to identify host determinants of enteric calicivirus infection using CRISPR-Cas9
genome wide screening. We recently identified a functional ReCV entry receptor that is necessary for ReCV
permissiveness in cell culture. We hypothesize that the ReCV entry receptor is also involved in HuNoV
infections. This hypothesis will be tested in the following specific aims. Aim 1. Characterize receptor mediated
ReCV infection. Aim 2: Comparative characterization of HuNoV and ReCV infections in enteroid and B cell
cultures. In the first aim we will dissect the role of HBGAs in ReCV receptor mediated entry by using ReCV
isolates with disctinct HBGA binding, cell lines expressing different HBGAs and/or the receptor, Enterobacter
SENG-6 EPS and different synthetic HBGAs. We will also evaluate the role of the different transmembrane
isoforms of the receptor in infection and map the ReCV interaction site and importance of glycosylation. In the
second aim, we will evaluate the role of ReCV entry receptor in HuNoV infections in enteroid and B cell
cultures and identify other cell surface components playing a role in HuNoV infections. We will also evaluate
the mechanism of bile or bile salts in promoting HuNoV infections and the role of M cells in infections of
polarized cells. Our long-term goal is to identify and characterize viral and host determinants of ReCV and
HuNoV infections and to develop novel intervention/prevention strategies. Our proposal uses a novel enteric
calicivirus model to understand viral entry and the role of bile and HBGAs in enteric viral infections. Our
findings with ReCVs may be directly transferable to HuNoV infection. The major significance of this project is
the identification of determinants of susceptibility to enteric calicivirus infection that can lead to improved
HuNoV cell culture systems and new intervention/prevention strategies.

## Key facts

- **NIH application ID:** 10876231
- **Project number:** 5R01AI139307-06
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** TIBOR FARKAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $373,214
- **Award type:** 5
- **Project period:** 2019-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876231

## Citation

> US National Institutes of Health, RePORTER application 10876231, Determinants of Enteric Calicivirus Infection. (5R01AI139307-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10876231. Licensed CC0.

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