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Journal Article Ppublish 15 citations

PubMed: 35789750 DOI: 10.1016/j.isci.2022.104685

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

iScience 25(8):104685

Authors: 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

Affiliations

  • Department of Immunology and Nano-Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA.
  • Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
  • Department of Pharmacology, University of South Alabama, Mobile, AL 36688, USA.
  • Department of Physics, Florida International University, Miami, FL 33199, USA.
  • Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA.
  • Miller School of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Miami, Miami, FL 33136, USA.

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 , , , and inflammatory factors; and  mucins; and , , and transcription factors in COVID-19 patient nasal samples compared with uninfected controls. A lncRNA on antisense strand to ICAM-1 or 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 lncRNA. Notably, blocking lncRNA reduced the SARS-CoV-2 replication and suppressed MUC5AC mucin levels and associated inflammation, and select -dependent miRNAs (e.g., let-7b-5p and miR-200a-5p) were implicated. Thus, lncRNA represents an essential facilitator of SARS-CoV-2 infection and associated airway mucoinflammatory response.

MeSH

Mucins, Infections, Rna, Viral, Phenotype, Sars Virus, Intercellular Adhesion Molecule-1, Rna, Long Noncoding, Covid-19, Sars-Cov-2

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