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Front Immunol . SARS-CoV-2-Encoded MiRNAs Inhibit Host Type I Interferon Pathway and Mediate Allelic Differential Expression of Susceptible Gene

tetano

Editor, Senior Moderator
Front Immunol


. 2021 Dec 23;12:767726.
doi: 10.3389/fimmu.2021.767726. eCollection 2021.
SARS-CoV-2-Encoded MiRNAs Inhibit Host Type I Interferon Pathway and Mediate Allelic Differential Expression of Susceptible Gene


Youwei Zhu[SUP] 1 [/SUP], Zhaoyang Zhang[SUP] 1 [/SUP], Jia Song[SUP] 2 [/SUP], Weizhou Qian[SUP] 2 [/SUP], Xiangqian Gu[SUP] 3 [/SUP], Chaoyong Yang[SUP] 2 4 [/SUP], Nan Shen[SUP] 5 6 7 [/SUP], Feng Xue[SUP] 8 [/SUP], Yuanjia Tang[SUP] 1 5 [/SUP]



Affiliations

Abstract

Infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the rapid spread of coronavirus disease 2019 (COVID-19), has generated a public health crisis worldwide. The molecular mechanisms of SARS-CoV-2 infection and virus-host interactions are still unclear. In this study, we identified four unique microRNA-like small RNAs encoded by SARS-CoV-2. SCV2-miR-ORF1ab-1-3p and SCV2-miR-ORF1ab-2-5p play an important role in evasion of type I interferon response through targeting several genes in type I interferon signaling pathway. Particularly worth mentioning is that highly expressed SCV2-miR-ORF1ab-2-5p inhibits some key genes in the host innate immune response, such as IRF7, IRF9, STAT2, OAS1, and OAS2. SCV2-miR-ORF1ab-2-5p has also been found to mediate allelic differential expression of COVID-19-susceptible gene OAS1. In conclusion, these results suggest that SARS-CoV-2 uses its miRNAs to evade the type I interferon response and links the functional viral sequence to the susceptible genetic background of the host.

Keywords: COVID-19; SARS-CoV-2; innate immune response; microRNA (miRNA); single-nucleotide polymorphisms (SNPs); type I interferon pathway.
 
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