Innate immune responses to SARS-CoV-2 infection in the olfactory epithelium

NIH Pandemic-Era Grants

Pandemic Era Grants

2023

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Principal Investigator: Qizhi  Gong
Organization: UNIVERSITY OF CALIFORNIA AT DAVIS
Fiscal Year: 2023
Award: $590,077
Funding agency: National Institute on Deafness and Other Communication Disorders

RESEARCH SUMMARY
Sudden-onset of olfactory loss has been recognized as a common COVID-19 symptom. The mechanism of
COVID-19 related olfactory dysfunction is unknown. Whether the degree of olfactory deficit is indicative of any
long-term neurological diseases in COVID-19 has not been evaluated. Recent single-cell RNA-seq analyses
revealed that the receptor for SARS-CoV-2, ACE2, is not expressed by olfactory sensory neurons (OSNs) but
are expressed by supporting sustentacular (Sus) cells in the OE. Therefore, Sus cells may be the entry cell
type for SARS-CoV-2 in the OE. SARS-CoV-2 infection in the OE needs to be further characterized. Current
observations indicate that the viral infection is sparse and localized. Widespread olfactory receptor
downregulation has been reported under viral infection suggesting that there might be a distributed viral impact
from localized viral infection in the OE. We hypothesize that widespread Sus cell mediated inflammatory
response, triggered by SARS-CoV-2, is responsible for COVID-19 associated olfactory loss. In this study, we
will characterize inflammatory responses to SARS-CoV-2 in the olfactory epithelium and identify Sus cell
specific cytokine expressions; we will established a primary Sus cell culture system to examine viral
recognition pathways and transcription factors involved in SARS-CoV-2 induced innate immune responses; we
will further determine SARS-CoV-2 infection induced olfactory sensory neuron functional deficits. Through this
study, we will gain mechanistic insight into COVID-19 associated olfactory loss.

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Drosophila TOLL><Homologous Chemotactic Cytokines><Human><Immune><Immunes><Infection><Inflammation><Inflammatory Response><Innate Immune Response><Intercrines><Intracellular Communication and Signaling><K-18><K-18 conjugate><K18><K18 combination><Mediating><Mice><Mice Mammals><Microbe><Modern Man><Molecular><Mouse Strains><Murine><Mus><Nasal><Nasal Passages Nose><Nerve Cells><Nerve Unit><Nervous System Diseases><Neural Cell><Neurocyte><Neurologic Disorders><Neurologic Manifestations><Neurologic Signs and Symptoms><Neurologic Symptoms><Neurological Disorders><Neurological Manifestations><Neurological Signs and Symptoms><Neuronal Dysfunction><Neurons><Nose><Olfactory Epithelium><Olfactory Mucosa><Olfactory dysfunction><Pathogenicity><Pathway interactions><Patients><Process><Receptor Down-Regulation><Receptor Protein><Regulation><Reporter Genes><Reporting><Research><Respiratory System, Nose, Nasal Passages><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 positive><SARS-CoV-2 positivity><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SIS cytokines><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 positive><Severe acute respiratory syndrome coronavirus 2 positivity><Severe acute respiratory syndrome related corona virus 2><Signal Transduction><Signal Transduction Systems><Signaling><Strains Cell Lines><Symptoms><TLR4><TLR4 gene><Testing><Thick><Thickness><Tissues><Toll Homologue><Transcript><Transcription Factor Proto-Oncogene><Transcription factor genes><Transgenic Organisms><Viral><Viral Diseases><Virus Diseases><Virus Replication><Wuhan coronavirus><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><angiotensin converting enzyme 2><angiotensin converting enzyme II><anosphrasia><biological signal transduction><cell culture><cell cultures><cell type><chemoattractant cytokine><chemokine><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 positive><coronavirus disease 2019 positivity><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><cribriform plate><cultured cell line><cytokine><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><gene manipulation><genetic manipulation><genetically manipulate><genetically perturb><hCoV19><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><innate immune function><insight><loss of smell><model of animal><mouse model><murine model><nCoV2><nervous system disorder><neural dysfunction><neural manifestation><neuroepithelium><neurological disease><neuronal><novel><olfactory bulb><olfactory impairment><olfactory loss><olfactory receptor><olfactory sensory neurons><pathogenic virus><pathway><permissiveness><post SARS-CoV-2 infection><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><receptor><receptor downregulation><receptor expression><response><scRNA-seq><seal><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><sustentacular cell><toll-like receptor 4><transcription factor><transgenic><viral infection><viral multiplication><viral pathogen><viral replication><virus infection><virus multiplication><virus pathogen><virus-induced disease>