# Human coronavirus infection of the nasal epithelium

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $727,886

## Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 emerged in China in late 2019, resulting in the
COVID-19 pandemic. Like SARS-CoV (2002) and Middle East respiratory syndrome (MERS)-CoV (2012),
SARS-CoV-2 can progress to cause lethal pneumonia. In contrast, infections with “common” respiratory CoVs
(NL63, 229E, OC43) are largely limited to the upper respiratory tract. Furthermore, SARS-CoV-2 and in particular
the omicron variant, can sometimes cause primarily upper respiratory infections. Thus, despite their highly
conserved genome structure and shared replication schemes, human CoVs induce varying degrees of disease.
Respiratory CoVs initiate infection through the nose, though few studies have addressed CoV infection of the
nasal epithelium. We have an established cryobank of nasal epithelial cells from over 1000 genetically
characterized individuals capable of being expanded and grown as air liquid interface (ALI) cultures,
recapitulating the nasal respiratory epithelium. Our preliminary studies demonstrate that SARS-2 (and its
emerging variants), MERS and NL63 all productively infect these cultures. However, NL63 only replicates at a
lower temperature (33C), infects single cells rather than clusters (evinced by SARS-2/MERS) and causes a more
cytopathic effect than SARS-2 or MERS, suggesting it may induce a robust local immune response thereby
limiting its replication to the upper respiratory tract or stimulating an adaptive immune response prior to infecting
the lower airway. One COVID-19 risk locus includes the leucine zipper transcription factor-like 1 gene (LZTFL1),
which we show is highly expressed in ciliated nasal cells, with ubiquitous expression throughout the cytoplasm.
Our preliminary data of SARS-CoV-2 infected cultures genotyped for the high vs low-risk LZTFL1 polymorphisms
demonstrate that LZTFL1 could play a role in variability of SARS-CoV-2 spread. In addition, polymorphisms in
OAS1, a sensor of double-stranded viral RNA that initiates the antiviral RNase L pathway, have been linked to
COVID-19 resistance. We have extensive experience in this pathway and recently reported that SARS-CoV-2
activates RNase L while MERS-CoV shuts it down. Based on these and other data, we hypothesize that
pathogenic outcomes of CoV infections are reflected in viral biology in the nasal epithelium. Thus, using
a battery of diverse CoVs we will assess differences in cell entry and spread, optimal temperature for viral
replication and shedding as well as host nasal cell responses to each CoV. We propose to use our biobank
to identify host and viral factors affecting the establishment of infection, host cytokine and nasal antiviral
responses and the contribution of polymorphisms in LZTFL1 and OAS1 genes in the outcome of infection. Our
complementary expertise in coronavirus biology (Weiss) and nasal pathophysiology (Cohen) uniquely positions
us to address these Aims. This work will contribute to understanding nasal CoV infection, the divergence...

## Key facts

- **NIH application ID:** 10596044
- **Project number:** 1R01AI169537-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Noam A Cohen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $727,886
- **Award type:** 1
- **Project period:** 2022-09-20 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596044

## Citation

> US National Institutes of Health, RePORTER application 10596044, Human coronavirus infection of the nasal epithelium (1R01AI169537-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10596044. Licensed CC0.

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