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 mechanism 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 own microRNAs to evade the type I interferon response, and links the functional viral sequence to the susceptible genetic background of the host. Key words: SARS-CoV-2, COVID-19, microRNA (microRNA), innate immune response, type I interferon pathway, single-nucleotide polymorphisms (SNPs)
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