Published on Thu Sep 09 2021

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

Singh, M., Chazal, M., Quarato, P., Bourdon, L., Malabat, C., Vallet, T., Vignuzzi, M., van der Werf, S., Behillil, S., Donati, F., Sauvonnet, N., Nigro, G., Bourgine, M., Jouvenet, N., Cecere, G.

SARS-CoV-2 infection results in impaired interferon response in severe COVID-19 patients. We sequenced small RNAs from SARS- cov-2-infected human cells and identified a micro RNA (miRNA) encoded in a recently evolved region of

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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 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 employs a virus-encoded miRNA to hijack the host miRNA machinery and evade the interferon-mediated immune response.