A virus-derived microRNA targets immune response genes during SARS-CoV-2 infection.
Meetali Singh, Maxime Chazal, Piergiuseppe Quarato, Loan Bourdon, Christophe Malabat, Thomas Vallet, Marco Vignuzzi, Sylvie van der Werf, Sylvie Behillil, Flora Donati, Nathalie Sauvonnet, Giulia Nigro, Maryline Bourgine, Nolwenn Jouvenet, Germano Cecere
Author Information
Meetali Singh: Department of Developmental and Stem Cell Biology, Institut Pasteur, CNRS UMR3738, Mechanisms of Epigenetic Inheritance, Universit�� de Paris, Paris, France. ORCID
Maxime Chazal: Virus Sensing and Signaling Unit, Institut Pasteur, CNRS UMR3569, Universit�� de Paris, Paris, France. ORCID
Piergiuseppe Quarato: Department of Developmental and Stem Cell Biology, Institut Pasteur, CNRS UMR3738, Mechanisms of Epigenetic Inheritance, Universit�� de Paris, Paris, France. ORCID
Loan Bourdon: Department of Developmental and Stem Cell Biology, Institut Pasteur, CNRS UMR3738, Mechanisms of Epigenetic Inheritance, Universit�� de Paris, Paris, France.
Christophe Malabat: Department of Computational Biology, Institut Pasteur, Bioinformatics and Biostatistics Hub, Universit�� de Paris, Paris, France.
Thomas Vallet: Viral Populations and Pathogenesis Unit, Institut Pasteur, CNRS UMR 3569, Universit�� de Paris, Paris, France. ORCID
Marco Vignuzzi: Viral Populations and Pathogenesis Unit, Institut Pasteur, CNRS UMR 3569, Universit�� de Paris, Paris, France.
Sylvie van der Werf: National Reference Center for Respiratory Viruses, Molecular Genetics of RNA Viruses, Institut Pasteur, CNRS UMR 3569, Universit�� de Paris, Paris, France. ORCID
Sylvie Behillil: National Reference Center for Respiratory Viruses, Molecular Genetics of RNA Viruses, Institut Pasteur, CNRS UMR 3569, Universit�� de Paris, Paris, France.
Flora Donati: National Reference Center for Respiratory Viruses, Molecular Genetics of RNA Viruses, Institut Pasteur, CNRS UMR 3569, Universit�� de Paris, Paris, France. ORCID
Nathalie Sauvonnet: Intracellular Trafficking and Tissue Homeostasis, Institut Pasteur, Universit�� de Paris, Paris, France. ORCID
Giulia Nigro: Microenvironment and Immunity Unit, Institut Pasteur, INSERM U1224, Universit�� de Paris, Paris, France.
Maryline Bourgine: Virology Department, Institut Pasteur, Institut Pasteur-TheraVectys Joint Lab, Universit�� de Paris, Paris, France. ORCID
Nolwenn Jouvenet: Virus Sensing and Signaling Unit, Institut Pasteur, CNRS UMR3569, Universit�� de Paris, Paris, France. ORCID
Germano Cecere: Department of Developmental and Stem Cell Biology, Institut Pasteur, CNRS UMR3738, Mechanisms of Epigenetic Inheritance, Universit�� de Paris, Paris, France. ORCID
SARS-CoV-2 infection results in impaired interferon response in patients with severe COVID-19. However, how SARS-CoV-2 interferes with host immune responses is incompletely understood. Here, we sequence small RNAs from SARS-CoV-2-infected human cells and identify a microRNA (miRNA) derived from a recently evolved region of the viral genome. We show that the virus-derived miRNA produces two miRNA isoforms in infected cells by the enzyme Dicer, which are loaded into Argonaute proteins. Moreover, the predominant miRNA isoform targets the 3'UTR of interferon-stimulated genes and represses their expression in a miRNA-like fashion. Finally, the two viral miRNA isoforms were detected in nasopharyngeal swabs from COVID-19 patients. We propose that SARS-CoV-2 can potentially employ a virus-derived miRNA to hijack the host miRNA machinery, which could help to evade the interferon-mediated immune response.
