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

Autor: Kannan A; Department of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland.; Neurimmune AG, Wagistrasse 18, 8952 Schlieren, Switzerland., Suomalainen M; Department of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland., Volle R; Department of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland., Bauer M; Department of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland.; Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA., Amsler M; Department of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland., Trinh HV; Department of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland.; Genezen, 9900 Westpoint Dr, Suite 128, Indianapolis, IN 46256, USA., Vavassori S; Division of Immunology, University Children's Hospital Zürich, 8032 Zürich, Switzerland., Schmid JP; Division of Immunology, University Children's Hospital Zürich, 8032 Zürich, Switzerland.; Faculty of Medicine, University of Zürich, 8006 Zürich, Switzerland., Vilhena G; 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., Marín-González A; Department of Macromolecular Structures, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Cantoblanco, E-28049 Madrid, Spain., Perez R; 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., Franceschini A; Department of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland.; Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia, 20139 Milano, Italy.; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland., Mering CV; Department of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland.; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland., Hemmi S; Department of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland., Greber UF; Department of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2022 Jun 28; Vol. 14 (7). Date of Electronic Publication: 2022 Jun 28.
DOI: 10.3390/v14071407
Abstrakt: 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.
Databáze: MEDLINE
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