A virus-encoded microRNA contributes to evade innate immune response 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

doi:10.15252/embr.202154341

Molecular BiologyEMBO ReportsDec 16, 2021

Peer-reviewed journal article

A virus-encoded microRNA contributes to evade innate immune response during SARS-CoV-2 infection

Meetali Singh iD, Maxime Chazal iD, Piergiuseppe Quarato iD, Loan Bourdon iD, Christophe Malabat iD, Thomas Vallet iD, Marco Vignuzzi iD, Sylvie van der Werf iD, Sylvie Behillil iD, Flora Donati iD, Nathalie Sauvonnet iD, Giulia Nigro iD, Maryline Bourgine iD, Nolwenn Jouvenet iD, Germano Cecere iD

Abstract

SARS-CoV-2 infection results in impaired interferon response in severe COVID-19 patients. However, how SARS-CoV-2 interferes with host immune response is incompletely understood. Here, we sequenced small RNAs from SARS-CoV-2-infected human cells and identified a micro-RNA (miRNA) encoded in a recently evolved region of the viral genome. We show that the virus-encoded miRNA produces two miRNA isoforms in infected cells by the enzyme Dicer and they are loaded into Argonaute proteins. Moreover, the predominant miRNA isoform targets the 3UTR 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 employs a virus-encoded miRNA to hijack the host miRNA machinery and evade the interferon-mediated immune response.

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