# Molecular Biology of RV-C and its Asthma-related Receptor, CDHR3

> **NIH NIH U19** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $334,981

## Abstract

PROJECT SUMMARY/ABSTRACT
Asthma is a highly complex disease because individual etiologies result from composite elements of genetic
susceptibility, personal medical histories and a myriad of environmental factors. This Program will collect and
evaluate data relevant to each component. Project II contributes experience and technologies to describe the
molecular mechanisms by which virus infections, specifically by human rhinoviruses (RV), contribute and
shape episodes of asthma. Canonically linked to the common cold, RV infections contribute 50-85% of asthma
exacerbations and are the most frequently isolated viruses during the most severe respiratory infections and
hospitalizations among children. More so than RV-A&B isolates, viruses in the RV-C species are particularly
linked to illnesses in early childhood, and their infections are strongly linked to subsequent development of
asthma. The RV-C require cadherin-related family member 3 (CDHR3), an unusual airway-specific protein, as
their cell-entry receptor. The “A” allele of this gene (Tyr529 protein variant) is among the strongest known
genetic correlates for a type of childhood asthma marked by severe episodic wheezing. Conversely, Cys529,
encoded by the “G” allele, and of much higher prevalence in modern human lineages, is not an asthma
correlate. Our fundamental hypothesis is that the CDHR3 Cys529 variant fails at the biochemical level to display
this protein properly or extensively on cell surfaces, making their carriers more refractive to RV-C infections
and virus-induced asthma-exacerbations. The three Aims of the Project will examine the structure,
biochemistry and function of CDHR3 in recombinant, cell culture and native tissue formats. The expected
information includes (a) a cryoEM structure determination of the receptor:RV-C complex, (b) cryoEM structure
determinations of RV-C complexed with neutralizing and non-neutralizing antibodies, (c) biochemical
descriptions of CDHR3 requirements for differential cell surface display (Cys/Tyr529), (d) biochemical
descriptions of CDHR3 glycosylation sites, dimerization sites and virus interaction sites. We will also examine
primary tissue, and tissue-derived differentiated cell cultures (e.g. ALI), to validate and localize the sites of
CDHR3 display and determine how the genetics-determined allele (“A” vs “G”) confers susceptibility to RV-C
infections. Our techniques and assays will also document for the first time, if and how common environmental
factors, such as an individual's microbiome content, may influence the extent and severity of RV infections by
altering RV receptor expression or a cell's infection susceptibility in its native primary context.

## Key facts

- **NIH application ID:** 9858219
- **Project number:** 5U19AI104317-08
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** ANN C. PALMENBERG
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,981
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858219

## Citation

> US National Institutes of Health, RePORTER application 9858219, Molecular Biology of RV-C and its Asthma-related Receptor, CDHR3 (5U19AI104317-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9858219. Licensed CC0.

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