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

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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number104685
JournaliScience
Volume25
Issue number8
DOIs
StatePublished - Aug 19 2022

Keywords

  • Immunology
  • Molecular biology
  • Molecular mechanism of gene regulation
  • Virology

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Immunomodulatory LncRNA on antisense strand of ICAM-1 augments SARS-CoV-2 infection-associated airway mucoinflammatory phenotype'. Together they form a unique fingerprint.

Cite this