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Publications

Journal Article Research Support, Non-U.S. Gov't Epublish 1 citation

PubMed: 35891387 DOI: 10.3390/v14071407

Sequence-Specific Features of Short Double-Strand, Blunt-End RNAs Have RIG-I- and Type 1 Interferon-Dependent or -Independent Anti-Viral Effects.

Viruses 14(7)

Authors: Abhilash Kannan, Maarit Suomalainen, Romain Volle, Michael Bauer, Marco Amsler, Hung V Trinh, Stefano Vavassori, Jana Pachlopnik Schmid, Guilherme Vilhena, Alberto Marín-González, Ruben Perez, Andrea Franceschini, Christian von Mering, Silvio Hemmi, Urs F Greber

Affiliations

  • Department of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland.
  • Neurimmune AG, Wagistrasse 18, 8952 Schlieren, Switzerland.
  • Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • Genezen, 9900 Westpoint Dr, Suite 128, Indianapolis, IN 46256, USA.
  • Division of Immunology, University Children's Hospital Zürich, 8032 Zürich, Switzerland.
  • Faculty of Medicine, University of Zürich, 8006 Zürich, Switzerland.
  • Departamento de Física Teórica de la Materia Condensada, Universidad Autónoma de Madrid, E-28049 Madrid, Spain. Condensed Matter Physics Center (IFIMAC), Universidad Autónoma de Madrid, E-28049 Madrid, Spain.
  • Department of Macromolecular Structures, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Cantoblanco, E-28049 Madrid, Spain.
  • Departamento de Física Teórica de la Materia Condensada, Universidad Autónoma de Madrid, E-28049 Madrid, Spain.
  • Condensed Matter Physics Center (IFIMAC), Universidad Autónoma de Madrid, E-28049 Madrid, Spain.
  • Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia, 20139 Milano, Italy.
  • Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.

Abstract

Pathogen-associated molecular patterns, including cytoplasmic DNA and double-strand (ds)RNA trigger the induction of interferon (IFN) and antiviral states protecting cells and organisms from pathogens. Here we discovered that the transfection of human airway cell lines or non-transformed fibroblasts with 24mer dsRNA mimicking the cellular micro-RNA (miR)29b-1* gives strong anti-viral effects against human adenovirus type 5 (AdV-C5), influenza A virus X31 (H3N2), and SARS-CoV-2. These anti-viral effects required blunt-end complementary RNA strands and were not elicited by corresponding single-strand RNAs. dsRNA miR-29b-1* but not randomized miR-29b-1* mimics induced IFN-stimulated gene expression, and downregulated cell adhesion and cell cycle genes, as indicated by transcriptomics and IFN-I responsive Mx1-promoter activity assays. The inhibition of AdV-C5 infection with miR-29b-1* mimic depended on the IFN-alpha receptor 2 (IFNAR2) and the RNA-helicase retinoic acid-inducible gene I (RIG-I) but not cytoplasmic RNA sensors MDA5 and ZNFX1 or MyD88/TRIF adaptors. The antiviral effects of miR29b-1* were independent of a central AUAU-motif inducing dsRNA bending, as mimics with disrupted AUAU-motif were anti-viral in normal but not RIG-I knock-out (KO) or IFNAR2-KO cells. The screening of a library of scrambled short dsRNA sequences identified also anti-viral mimics functioning independently of RIG-I and IFNAR2, thus exemplifying the diverse anti-viral mechanisms of short blunt-end dsRNAs.

MeSH

Infections, Rna, Adenoviridae, Antiviral Agents, Virology, Cells, Genes, Tretinoin, Orthomyxoviridae, Sars-Cov-2

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