Distinct Mucoinflammatory Phenotype and the Immunomodulatory Long Noncoding Transcripts Associated with SARS-CoV-2 Airway Infection
Other Scholarly Work
Devadoss, Dinesh, Acharya, Arpan, Manevski, Marko et al. (2021). Distinct Mucoinflammatory Phenotype and the Immunomodulatory Long Noncoding Transcripts Associated with SARS-CoV-2 Airway Infection
. 10.1101/2021.05.13.21257152
Devadoss, Dinesh, Acharya, Arpan, Manevski, Marko et al. (2021). Distinct Mucoinflammatory Phenotype and the Immunomodulatory Long Noncoding Transcripts Associated with SARS-CoV-2 Airway Infection
. 10.1101/2021.05.13.21257152
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 , and SCGB1A1 ) and respiratory mucins ( MUC5AC, MUC5B, MUC2 , and MUC4) , and differential modulation of select long noncoding RNAs (lncRNAs i.e., LASI, TOSL, NEAT1 , and MALAT1 ). 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 of IL-6, ICAM-1, SCGB1A1, SPDEF, MUC5AC, MUC5B , and MUC4 . Interestingly, LASI, TOSL , and NEAT1 lncRNA expressions were also markedly elevated in high-VL patients with no change in MALAT1 expression. In addition, dual-staining of LASI and SARS-CoV-2 nucleocapsid N1 RNA 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.
