Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Microbiological Testing Lab, Shanghai Pudong Center for Disease Control & Prevention, Shanghai, China.
Front Cell Infect Microbiol. 2023 Jun 2;13:1190870. doi: 10.3389/fcimb.2023.1190870. eCollection 2023.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a lasting threat to public health. To minimize the viral spread, it is essential to develop more reliable approaches for early diagnosis of the infection and immediate suppression of the viral replication. Herein, through computational prediction of SARS-CoV-2 genome and screening analysis of specimens from covid-19 patients, we predicted 15 precursors for SARS-CoV-2-encoded miRNAs (CvmiRNAs) containing 20 mature CvmiRNAs, in which CvmiR-2 was successfully detected by quantitative analysis in both serum and nasal swab samples of patients. CvmiR-2 showed high specificity in distinguishing covid-19 patients from normal controls, and high conservation between SARS-CoV-2 and its mutants. A positive correlation was observed between the CvmiR-2 expression level and the severity of patients. The biogenesis and expression of CvmiR-2 were validated in the pre-CvmiR-2-transfected A549 cells, showing a dose-dependent pattern. The sequence of CvmiR-2 was validated by sequencing analysis of human cells infected by either SARS-CoV-2 or pre-CvmiR-2. Target gene prediction analysis suggested CvmiR-2 may be involved in the regulation of the immune response, muscle pain and/or neurological disorders in covid-19 patients. In conclusion, the current study identified a novel v-miRNA encoded by SARS-CoV-2 upon infection of human cells, which holds the potential to serve as a diagnostic biomarker or a therapeutic target in clinic.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）已成为对公众健康的持久威胁。为了最大程度地减少病毒传播，开发更可靠的方法来早期诊断感染并立即抑制病毒复制至关重要。在此，我们通过对 SARS-CoV-2 基因组进行计算预测和对新冠病毒患者标本进行筛选分析，预测了包含 20 个成熟 CvmiRNA 的 15 个 SARS-CoV-2 编码 miRNA（CvmiRNA）前体，其中 CvmiR-2 通过对新冠患者血清和鼻腔拭子样本的定量分析成功检测到。CvmiR-2 在区分新冠患者与正常对照方面具有高度特异性，并且在 SARS-CoV-2 与其突变体之间具有高度保守性。CvmiR-2 的表达水平与患者的严重程度呈正相关。在转染前 CvmiR-2 的 A549 细胞中验证了 CvmiR-2 的生物发生和表达，显示出剂量依赖性模式。通过感染 SARS-CoV-2 或前 CvmiR-2 的人细胞的测序分析验证了 CvmiR-2 的序列。靶基因预测分析表明，CvmiR-2 可能参与新冠患者的免疫反应、肌肉疼痛和/或神经紊乱的调节。总之，本研究鉴定了一种新型由 SARS-CoV-2 在感染人细胞时编码的 v-miRNA，它有可能作为临床诊断生物标志物或治疗靶标。
