# Rhinovirus C Infection in Normal and Asthmatic Human Airway Epithelium at Single Cell Resolution

> **NIH NIH R21** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $256,674

## Abstract

SUMMARY
As the causative agents in a majority of recurrent respiratory virus infections and the most common trigger of
lung disease exacerbations, rhinoviruses are a major threat to public health and a significant economic burden.
There are no vaccines or direct-activating antiviral therapies available to prevent rhinovirus infection or mitigate
disease. Relative to other strains, rhinoviruses species C (RV-C) are associated with more severe disease,
especially in individuals with asthma. In addition, a single nucleotide polymorphism (SNP) in the gene encoding
CDHR3, a receptor for RV-C, was recently identified as a risk factor for severe asthma exacerbations.
However, as a recently identified pathogen, many aspects of RV-C biology, such as details of the host
response and the effects of CDHR3 genetic variation on infection dynamics remain undefined. Thus, the
overall goals of this application are to (i) define the host response to RV-C infection in both normal and
asthmatic human airway epithelium (HAE) and (ii) determine the impact of the CDHR3
rs6967330 SNP on
virus–host dynamics in physiological context. Our central hypotheses are that the innate immune response to
RV-C will be altered in asthmatic HAE compared to normal HAE, and that the CDHR3 rs6967330[A] risk allele
modifies this response by altering viral infectivity of ciliated cells.
We will test these hypotheses by pursuing
two Specific Aims: Aim 1 will define the host response to RV-C in normal and asthmatic HAE at single cell
resolution; Aim 2 will determine the contribution of the CDHR3 asthma risk allele to RV-C infection and host
response. Our research plan builds upon an ongoing collaboration between the Scull and Rosenberg
laboratories and is both conceptually and technically innovative in its integration of HAE culture models and
single cell RNA-Seq to explore the physiologically-relevant host response to RV-C at unprecedented
resolution. Furthermore, we propose novel gene editing experiments that will directly determine how CDHR3
genetic variation
affects
RV-C infection in primary HAE on an isogenic background. This work is significant as
our results will have broad implications for understanding the roles of specific airway epithelial cell types in the
antiviral response and specifically address how underlying disease status and host genotype impact
susceptibility to RV-C.

## Key facts

- **NIH application ID:** 9979166
- **Project number:** 1R21AI149180-01A1
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Brad Rosenberg
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $256,674
- **Award type:** 1
- **Project period:** 2020-01-24 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979166

## Citation

> US National Institutes of Health, RePORTER application 9979166, Rhinovirus C Infection in Normal and Asthmatic Human Airway Epithelium at Single Cell Resolution (1R21AI149180-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9979166. Licensed CC0.

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