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Differential regulation of viral entry-associated genes modulated by inflammatory cytokines in the nasal epithelium.
- Source :
-
Journal of medical virology [J Med Virol] 2024 Sep; Vol. 96 (9), pp. e29913. - Publication Year :
- 2024
-
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-α (TNF-α), and interferon-γ (IFN-γ). Specifically, ACE2 significantly decreased in type 2 cytokines (IL-4 and IL-13), while TMPRSS2 significantly decreased in type 1 cytokines (TNF-α and IFN-γ). 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-γ. 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.<br /> (© 2024 Wiley Periodicals LLC.)
- Subjects :
- Humans
Adult
Male
Female
Middle Aged
Angiotensin-Converting Enzyme 2 genetics
Angiotensin-Converting Enzyme 2 metabolism
Sinusitis virology
Sinusitis genetics
Sinusitis immunology
SARS-CoV-2 immunology
Rhinitis virology
Rhinitis genetics
Rhinitis immunology
Gene Expression Regulation
Serine Endopeptidases genetics
Serine Endopeptidases metabolism
COVID-19 immunology
COVID-19 virology
Coronavirus 229E, Human genetics
Dipeptidyl Peptidase 4 genetics
Dipeptidyl Peptidase 4 metabolism
Middle East Respiratory Syndrome Coronavirus genetics
Middle East Respiratory Syndrome Coronavirus immunology
Cytokines genetics
Cytokines metabolism
Nasal Mucosa virology
Virus Internalization
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9071
- Volume :
- 96
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of medical virology
- Publication Type :
- Academic Journal
- Accession number :
- 39257039
- Full Text :
- https://doi.org/10.1002/jmv.29913