Sequence-specific features of short double-strand, blunt-end RNAs have RIG-I- and type 1 interferon-dependent or -independent anti-viral effects
AuthorKannan, Abhilash; Suomalainen, Maarit; Volle, Romain; Bauer, Michael; Amsle, Marco; Trinh, Hung V.; Vavassor, Stefano; Pachlopnik Schmid, Jana; Vilhena Albuquerque D'Orey, José Guilherme; Marín-González, Alberto; Pérez Pérez, Rubén; Franceschini, Andrea; Mering, Christian von; Hemmi, Silvio; Greber, Urs F.
EntityUAM. Departamento de Física de la Materia Condensada
10.3390/v14071407Viruses 14.7 (2022): 1407
SubjectsAlpha2 Interferon; DNA Polymerase; MicroRNA 29b; Small Interfering RNA; Interferon Induced Helicase C; Myeloid Differentiation Factor 88; Física
Rights© 2022 by the authors
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
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
Google Scholar:Kannan, Abhilash - Suomalainen, Maarit - Volle, Romain - Bauer, Michael - Amsle, Marco - Trinh, Hung V. - Vavassor, Stefano - Pachlopnik Schmid, Jana - Vilhena Albuquerque D'Orey, José Guilherme - Marín-González, Alberto - Pérez Pérez, Rubén - Franceschini, Andrea - Mering, Christian von - Hemmi, Silvio - Greber, Urs F.
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