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

Youwei Zhu,Weizhou Qian,Jia Song,Yuanjia Tang,Xiangqian Gu,Feng Xue,Zhaoyang Zhang,Nan Shen,Chaoyong Yang

doi:10.3389/fimmu.2021.767726

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.

Highlights

The unprecedented worldwide outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a global health emergency
We found that SARS-CoV-2 produced small RNAs that were accumulating after the virus infection, especially in the 24-h infection treatment group (Figure 1A)
Soon after the outbreak of COVID-19, scientists quickly read the sequence of the SARS-CoV-2 genome RNA, which consists of about 30,000 bases

Summary

Introduction

The unprecedented worldwide outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a global health emergency. Extensive evidence and considerable efforts have revealed that COVID-19 is a systemic disease having the host innate immune response starting when the viral products are recognized by the host cell pattern recognition receptors, including Toll-like receptors and RIG-Ilike receptors [9,10,11]. This results in the production of interferon (IFN)-I and other IFN-stimulated genes (ISGs), especially the OAS gene family (OAS1, OAS2, and OAS3), which have been found to degrade a series of the viral genome. The results obtained by different bioinformatics tools are inconsistent, and this is affecting the understanding of the link between SARS-CoV-2 and functional miRNA production

Methods

Results

Conclusion