A virus‐derived microRNA targets immune response genes during SARS‐CoV‐2 infection

Meetali Singh (1) , Maxime Chazal (2) , Piergiuseppe Quarato (1) , Loan Bourdon (1) , Christophe Malabat (3) , Thomas Vallet (4) , Marco Vignuzzi (4) , Sylvie van Der Werf (5, 6) , Sylvie Behillil (5, 6) , Flora Donati (5, 6) , Nathalie Sauvonnet (7) , Giulia Nigro (8) , Maryline Bourgine (9) , Nolwenn Jouvenet (2) , Germano Cecere (1)

1 Mécanismes de l'Hérédité épigénétique / Mechanisms of epigenetic inheritance
2 Signalisation antivirale - Virus sensing and signaling
3 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
4 Populations virales et Pathogenèse - Viral Populations and Pathogenesis
5 GMV-ARN (UMR_3569 / U-Pasteur_2) - Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses
6 CNR - laboratoire coordonnateur - Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris]
7 BCI - Département de Biologie cellulaire et infection - Department of Cell Biology and infection
8 Microenvironnement et Immunité - Microenvironment and Immunity
9 Laboratoire commun Pasteur-TheraVectys

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.

Mots clés: Argonaute; COVID-19; SARS-CoV-2; interferon response; miRNA

Domaines: Sciences du Vivant [q-bio]

Meetali Singh, Maxime Chazal, Piergiuseppe Quarato, Loan Bourdon, Christophe Malabat, et al.. A virus‐derived microRNA targets immune response genes during SARS‐CoV‐2 infection. EMBO Reports, 2021, pp.e54341. ⟨10.15252/embr.202154341⟩. ⟨pasteur-03514377⟩