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Updated: Jul 19, 2025
Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions
Published on: September 22, 2023
Age-differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - Effects of vitamin
Francesca Sposito1, Shaun H Pennington2, Christopher A W David3
1Department of Women's & Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
Insights
Vitamin D may reduce SARS-CoV-2 infection by inhibiting TTLL-12 in adults. This study reveals age-related differences in airway epithelial responses to the virus, with vitamin D influencing interferon pathways.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Younger individuals and higher vitamin D levels correlate with reduced SARS-CoV-2 risk and better outcomes.
- Age-related differences in SARS-CoV-2 response and the role of vitamin D require further investigation.
Purpose of the Study:
- To investigate age-dependent mechanisms of SARS-CoV-2 response in airway epithelia.
- To elucidate the role of vitamin D in modulating these responses.
Main Methods:
- Culture of human nasal epithelial cells from children and adults at the air-liquid interface.
- Analysis of gene expression, DNA methylation, and protein interactions.
- In vitro assays including chromatin immunoprecipitation and luciferase reporter assays.
Main Results:
- Adult airway epithelia showed higher SARS-CoV-2 RNA recovery, linked to increased ANPEP/CD13 and reduced type I interferon.
- Vitamin D treatment in adult cells decreased TTLL-12 expression, a negative regulator of interferon.
- Vitamin D receptor binding to TTLL12 DNA was shown to involve DNA methyltransferase 1.
Conclusions:
- Age-related differences in CD13 and type I interferon expression influence upper airway epithelial susceptibility to SARS-CoV-2.
- Vitamin D demonstrates a molecular mechanism for reducing viral replication by inhibiting TTLL-12.
Abstract:
Young age and high vitamin D plasma levels have been associated with lower SARS-CoV-2 infection risk and favourable disease outcomes. This study investigated mechanisms associated with differential responses to SARS-CoV-2 across age groups and effects of vitamin D. Nasal epithelia were collected from healthy children and adults and cultured for four weeks at the air-liquid interface with and without vitamin D. Gene expression and DNA methylation were investigated. Surface protein expression was confirmed by immunofluorescence while vitamin D receptor recruitment to the DNA was analysed through chromatin immunoprecipitation. HEp-2 cells were used for protein co-immunoprecipitation and luciferase reporter assays. Compared to children, airway epithelia from adults show higher viral RNA recovery following infection. This was associated with higher ANPEP/CD13, reduced type I interferon expression, and differential DNA methylation. In cells from adults, exposure to vitamin D reduced TTLL-12 expression, a negative regulator of the interferon response. This was mediated by vitamin D receptor recruitment to TTLL12, where it instructs DNA methylation through DNA methyltransferase 1. This study links age-dependent differential expression of CD13 and type I interferon to variable infection of upper airway epithelia. Furthermore, it provides molecular evidence for vitamin D reducing viral replication by inhibiting TTLL-12.
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