# Viral Diversity and Pathogenesis of Mucosal Gastrointestinal and Respiratory Infections

> **NIH NIH U19** · BAYLOR COLLEGE OF MEDICINE · 2024 · $1,419,226

## Abstract

PROJECT SUMMARY
Acute gastrointestinal and respiratory infections are leading causes of morbidity and mortality in children
worldwide. Among gastrointestinal pathogens, human norovirus (HuNoV, NIAID category B pathogen) is the
leading cause of acute and sporadic gastroenteritis and is responsible for over 1 million pediatric health care
visits in the US each year. Respiratory syncytial virus (RSV, NIAID category C pathogen) is the major respiratory
pathogen in children globally and results in over 1.5 million health care visits annually in the US. In addition to
the clinical burden of disease, both viruses cause significant economic burden. There are currently no approved
vaccines for children for HuNoV or RSV. However, several vaccines and long-acting monoclonal antibodies are
in clinical trials or recently approved and are anticipated to be available to protect children. Immune pressure
driven changes in the genomic landscape of both viruses are anticipated with the introduction of interventions.
This is in addition to changes in the epidemiology following the COVID-19 pandemic which altered the burden of
disease and circulating patterns of these viruses, all posing challenges for the long-term success of interventions.
We propose to perform innovative and extensive sequencing of pediatric stool and respiratory samples from
racially and ethnically diverse population, together with functional validation in physiologically relevant pediatric
ex vivo organoid cultures, to identify viral and host factors affecting strain emergence and disease presentation.
Our studies will be focused on pediatric samples and organoids as children have long been considered a key
population for emergence of new HuNoV and RSV variants. Study samples will cover four distinct time periods:
pre-pandemic, pandemic, post-pandemic, and following the introduction of HuNoV and RSV interventions. The
studies are feasible since Project investigators are part of the CDC’s New Vaccine Surveillance Network that
evaluates the burden of pediatric gastrointestinal and respiratory illnesses in seven sites across the US, and
thus have access to thousands of relevant clinical samples and associated metadata. We will perform full-length
HuNoV and RSV genome analysis, microbiome, transcriptome, and virome analysis of clinical samples (Aim 1).
Study investigators have also established and characterized pediatric human intestinal and nasal organoids that
will serve as physiologically relevant models for functional studies (Aim 2).
Our proposed studies will provide a rich repository of genomic data and allow us to (i) track strain emergence
and diversity, (ii) discover biomarkers for mucosal gastrointestinal and respiratory disease, (iii) identify viral
signatures related to pathogenesis and strain emergence, and (iv) functionally delineate virus–host–microbiome
interactions. The timing of these studies is critical in the context of pandemic-induced epidemiological shifts and
the potential f...

## Key facts

- **NIH application ID:** 10855865
- **Project number:** 2U19AI144297-06
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Robert L. Atmar
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,419,226
- **Award type:** 2
- **Project period:** 2019-04-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10855865

## Citation

> US National Institutes of Health, RePORTER application 10855865, Viral Diversity and Pathogenesis of Mucosal Gastrointestinal and Respiratory Infections (2U19AI144297-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10855865. Licensed CC0.

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