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Differential regulation of viral entry-associated genes modulated by inflammatory cytokines in the nasal epithelium

Authors
 Hae Eun Noh  ;  Min-Seok Rha  ;  Yeonsu Jeong  ;  Dachan Kim  ;  Ju Hee Seo  ;  Miran Kang  ;  Uk Yeol Moon  ;  Chang-Hoon Kim  ;  Hyung-Ju Cho 
Citation
 JOURNAL OF MEDICAL VIROLOGY, Vol.96(9) : e29913, 2024-09 
Journal Title
JOURNAL OF MEDICAL VIROLOGY
ISSN
 0146-6615 
Issue Date
2024-09
MeSH
Adult ; Angiotensin-Converting Enzyme 2 / genetics ; Angiotensin-Converting Enzyme 2 / metabolism ; COVID-19 / immunology ; COVID-19 / virology ; Coronavirus 229E, Human / genetics ; Cytokines* / genetics ; Cytokines* / metabolism ; Dipeptidyl Peptidase 4 / genetics ; Dipeptidyl Peptidase 4 / metabolism ; Female ; Gene Expression Regulation ; Humans ; Male ; Middle Aged ; Middle East Respiratory Syndrome Coronavirus / genetics ; Middle East Respiratory Syndrome Coronavirus / immunology ; Nasal Mucosa* / virology ; Rhinitis / genetics ; Rhinitis / immunology ; Rhinitis / virology ; SARS-CoV-2 / immunology ; Serine Endopeptidases / genetics ; Serine Endopeptidases / metabolism ; Sinusitis / genetics ; Sinusitis / immunology ; Sinusitis / virology ; Virus Internalization*
Keywords
allergic rhinitis ; cytokines ; nasal epithelium ; sinusitis ; viral entry
Abstract
This study aimed to investigate the impact of different types of nasal inflammation on the regulation of entry-associated genes of respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus 229E (HCoV-229E), and influenza virus, in the nasal epithelium. Subjects were classified into three groups: control, eosinophilic chronic rhinosinusitis (ECRS), and noneosinophilic CRS (NECRS) groups. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), alanyl aminopeptidase (ANPEP), dipeptidyl peptidase 4 (DPP4), and beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1), and beta-galactoside alpha-2,3-sialyltransferase 4 (ST3GAL4) were selected as key entry-associated genes for SARS-CoV-2, HCoV-229E, MERS-CoV, and influenza, respectively, and were evaluated. Brushing samples obtained from each group and human nasal epithelial cells cultured using an air-liquid interface system were treated for 7 days with typical inflammatory cytokines and analyzed using real-time polymerase chain reaction. Western blot analysis and confocal microscopy were performed. The entry-associated genes showed distinct regulation patterns in response to each interleukin-4 (IL-4), interleukin-13 (IL-13), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). Specifically, ACE2 significantly decreased in type 2 cytokines (IL-4 and IL-13), while TMPRSS2 significantly decreased in type 1 cytokines (TNF-alpha and IFN-gamma). ANPEP significantly decreased in both types of cytokines. Remarkably, DPP4 significantly increased in type 2 cytokines and decreased in type 1 cytokines. Moreover, ST6GAL1 and ST3GAL4 significantly increased in type 2 cytokines and decreased in type 1 cytokines, particularly IFN-gamma. These findings were supported by western blot analysis and confocal imaging results, especially for ACE2 and DPP4. The findings regarding differential regulation suggest that patients with ECRS, primarily mediated by type 2 inflammation, may have lower susceptibility to SARS-CoV-2 and HCoV-229E infections but higher susceptibility to MERS-CoV and influenza infections.
Full Text
https://onlinelibrary.wiley.com/doi/10.1002/jmv.29913
DOI
10.1002/jmv.29913
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chang Hoon(김창훈) ORCID logo https://orcid.org/0000-0003-1238-6396
Rha, Min-Seok(나민석) ORCID logo https://orcid.org/0000-0003-1426-7534
Cho, Hyung Ju(조형주) ORCID logo https://orcid.org/0000-0002-2851-3225
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/201197
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