# Impact of Virome on Microbial Communities in the Respiratory Tract

> **NIH NIH R33** · DARTMOUTH COLLEGE · 2021 · $172,150

## Abstract

SUMMARY/ABSTRACT
 Respiratory viral infections contribute significantly to the morbidity and progressive decline in lung function
experienced by patients with chronic lung diseases, such as cystic fibrosis (CF). Respiratory viral infections
account for at least 50% of pulmonary exacerbations of adult CF patients and are linked to worsening of
pulmonary function, antibiotic use, prolonged hospitalizations and increased respiratory symptoms. Clinical
studies have also linked viral infections with the development of chronic infections, yet the underlying
mechanisms are unknown. In this proposal, we will test the novel hypothesis that viral exacerbations alter the
microbial composition of the upper and/or lower respiratory tract in CF, affecting both overall community diversity
and function and impairing pulmonary function. This study is innovative and exploratory in nature and intended
to lay the foundation for future studies to both uncover the molecular mechanisms underlying viral-bacterial
interactions in the respiratory tract during chronic lung disease and also inform larger clinical studies that assess
the impact of viral exacerbations on disease progression in CF and other chronic lung diseases.
 In the R61 phase of the award, we will use samples previously collected longitudinally over the course of one
year from the sinonasal cavity of CF patients during endoscopic surgery. In Aim 1, we will determine if viral
infections of the upper respiratory tract (URT) alter the microbial communities of the URT. In Aim 2, we will
investigate potential mechanisms by which viral infections shape the microbial composition of the URT, focusing
on skewed innate immune responses and altered nutritional immunity, as well as take an unbiased approach
using ribosome profiling to assess functional pathways activated during viral infection that might shift the
microbial communities of the URT.
 The R33 phase will build upon preliminary data and techniques adapted during the R61 phase to assess
how viral infections alter the microbiome composition and function throughout the respiratory tract and if these
alterations predict pulmonary function. Longitudinal, paired sinonasal and sputum samples will be collected every
three months for two years. In Aim 3, we will examine if viral infections shift the microbial communities of the
URT or LRT, as well as assess changes in innate immunity or nutritional immunity (i.e. elemental metals analysis)
or microbial pathways activated that predict pulmonary function decline during viral infection. This phase will
culminate in Aim 4 with mechanistic in vitro studies modeling key microbial interactions or pathways revealed in
Aim 3, using our unique polymicrobial infection models with primary sinonasal and bronchial epithelial cells from
CF patients.
 By elucidating mechanisms by which viral infections impact microbial communities in the respiratory tract,
our long-term goal is to identify new therapeutic targets for intervention...

## Key facts

- **NIH application ID:** 10806485
- **Project number:** 7R33HL137077-06
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Jennifer Melinda Bomberger
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $172,150
- **Award type:** 7
- **Project period:** 2017-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806485

## Citation

> US National Institutes of Health, RePORTER application 10806485, Impact of Virome on Microbial Communities in the Respiratory Tract (7R33HL137077-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10806485. Licensed CC0.

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