Immunomodulatory LncRNA on antisense strand of ICAM-1 augments SARS-CoV-2 infection-associated airway mucoinflammatory phenotype

Noncoding RNAs are important regulators of mucoinflammatory response, but little is known about the contribution of airway long noncoding RNAs (lncRNAs) in COVID-19. RNA-seq analysis showed a more than 4-fold increased expression of IL-6, ICAM-1, CXCL-8, and SCGB1A1 inflammatory factors; MUC5AC and ...

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Published in:iScience 2022-08, Vol.25 (8), p.104685-104685, Article 104685
Main Authors: Devadoss, Dinesh, Acharya, Arpan, Manevski, Marko, Houserova, Dominika, Cioffi, Michael D., Pandey, Kabita, Nair, Madhavan, Chapagain, Prem, Mirsaeidi, Mehdi, Borchert, Glen M., Byrareddy, Siddappa N., Chand, Hitendra S.
Format: Article
Language:English
Subjects:
Immunology
Molecular biology
Molecular mechanism of gene regulation
Virology
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Summary:Noncoding RNAs are important regulators of mucoinflammatory response, but little is known about the contribution of airway long noncoding RNAs (lncRNAs) in COVID-19. RNA-seq analysis showed a more than 4-fold increased expression of IL-6, ICAM-1, CXCL-8, and SCGB1A1 inflammatory factors; MUC5AC and MUC5B mucins; and SPDEF, FOXA3, and FOXJ1 transcription factors in COVID-19 patient nasal samples compared with uninfected controls. A lncRNA on antisense strand to ICAM-1 or LASI was induced 2-fold in COVID-19 patients, and its expression was directly correlated with viral loads. A SARS-CoV-2-infected 3D-airway model largely recapitulated these clinical findings. RNA microscopy and molecular modeling indicated a possible interaction between viral RNA and LASI lncRNA. Notably, blocking LASI lncRNA reduced the SARS-CoV-2 replication and suppressed MUC5AC mucin levels and associated inflammation, and select LASI-dependent miRNAs (e.g., let-7b-5p and miR-200a-5p) were implicated. Thus, LASI lncRNA represents an essential facilitator of SARS-CoV-2 infection and associated airway mucoinflammatory response. [Display omitted] •COVID19 airway mucoinflammatory response strongly correlates with LASI lncRNA level•Silencing LASI lncRNA suppresses SARS-CoV-2 viral load and associated inflammation•LASI lncRNA shows a potential direct interaction with SARS-CoV-2 spike viral RNA•Hosts of airway epithelial miRNAs are modulated by LASI to regulate inflammation Molecular biology; Molecular mechanism of gene regulation; Immunology; Virology
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2022.104685