Distinct Mucoinflammatory Phenotype and the Immunomodulatory Long Noncoding Transcripts Associated with SARS-CoV-2 Airway Infection
ABSTRACT Respiratory epithelial cells are the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the 3D human airway tissue model to evaluate innate epithelial cell responses to SARS-CoV-2 infection. A SARS-CoV-2 clinical isolate productively infected the 3D-airway model with a time-dependent increase in viral load (VL) and concurrent upregulation of airway immunomodulatory factors (IL-6, ICAM-1, andSCGB1A1) and respiratory mucins (MUC5AC, MUC5B, MUC2, andMUC4), and differential modulation of select long noncoding RNAs (lncRNAs i.e.,LASI, TOSL, NEAT1, andMALAT1). Next, we examined these immunomodulators in the COVID-19 patient nasopharyngeal swab samples collected from subjects with high- or low-VLs (∼100-fold difference). As compared to low-VL, high-VL patients had prominent mucoinflammatory signature with elevated expression ofIL-6, ICAM-1, SCGB1A1, SPDEF, MUC5AC, MUC5B, andMUC4. Interestingly,LASI, TOSL, andNEAT1lncRNA expressions were also markedly elevated in high-VL patients with no change inMALAT1expression. In addition, dual-staining ofLASIand SARS-CoV-2 nucleocapsidN1RNA showed predominantly nuclear/perinuclear localization at 24 hpi in 3D-airway model as well as in high-VL COVID-19 patient nasopharyngeal cells, which exhibited high MUC5AC immunopositivity. Collectively, these findings suggest SARS-CoV-2 induced lncRNAs may play a role in acute mucoinflammatory response observed in symptomatic COVID-19 patients..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 23. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Devadoss, Dinesh [VerfasserIn] |
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| doi: |
10.1101/2021.05.13.21257152 |
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| PPN (Katalog-ID): |
XBI02057066X |
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| 520 | |a ABSTRACT Respiratory epithelial cells are the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the 3D human airway tissue model to evaluate innate epithelial cell responses to SARS-CoV-2 infection. A SARS-CoV-2 clinical isolate productively infected the 3D-airway model with a time-dependent increase in viral load (VL) and concurrent upregulation of airway immunomodulatory factors (IL-6, ICAM-1, andSCGB1A1) and respiratory mucins (MUC5AC, MUC5B, MUC2, andMUC4), and differential modulation of select long noncoding RNAs (lncRNAs i.e.,LASI, TOSL, NEAT1, andMALAT1). Next, we examined these immunomodulators in the COVID-19 patient nasopharyngeal swab samples collected from subjects with high- or low-VLs (∼100-fold difference). As compared to low-VL, high-VL patients had prominent mucoinflammatory signature with elevated expression ofIL-6, ICAM-1, SCGB1A1, SPDEF, MUC5AC, MUC5B, andMUC4. Interestingly,LASI, TOSL, andNEAT1lncRNA expressions were also markedly elevated in high-VL patients with no change inMALAT1expression. In addition, dual-staining ofLASIand SARS-CoV-2 nucleocapsidN1RNA showed predominantly nuclear/perinuclear localization at 24 hpi in 3D-airway model as well as in high-VL COVID-19 patient nasopharyngeal cells, which exhibited high MUC5AC immunopositivity. Collectively, these findings suggest SARS-CoV-2 induced lncRNAs may play a role in acute mucoinflammatory response observed in symptomatic COVID-19 patients. | ||
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| 700 | 1 | |a Acharya, Arpan |e verfasserin |4 aut | |
| 700 | 1 | |a Manevski, Marko |e verfasserin |4 aut | |
| 700 | 1 | |a Pandey, Kabita |e verfasserin |4 aut | |
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| 700 | 1 | |a Chand, Hitendra S. |e verfasserin |0 (orcid)0000-0002-0574-9307 |4 aut | |
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