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

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

iScience (2022-07-06)
Dinesh Devadoss, Arpan Acharya, Marko Manevski, Dominika Houserova, Michael D Cioffi, Kabita Pandey, Madhavan Nair, Prem Chapagain, Mehdi Mirsaeidi, Glen M Borchert, Siddappa N Byrareddy, Hitendra S Chand
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Mucin MUC5AC Antibody, clone CLH2, clone CLH2, Chemicon®, from mouse
Sigma-Aldrich
Collagen from human placenta, Bornstein and Traub Type IV, powder, BioReagent, suitable for cell culture