Arslan Serdal, Bayyurt Burcu, Engin Aynur, Bakir Mehmet
Department of Medical Biology, Sivas Cumhuriyet University, Sivas, Turkey.
Department of Infectious Diseases and Clinical Microbiology, Sivas Cumhuriyet University, Sivas, Turkey.
J Med Virol. 2021 Aug;93(8):4729-4737. doi: 10.1002/jmv.26909. Epub 2021 Mar 14.
Crimean Congo hemorrhagic fever (CCHF) is one of the most important viral infections and is caused by Crimean Congo hemorrhagic fever orthonairovirus (CCHFV). Severity of CCHF can vary from a mild and nonspecific illness to a severe disease with fatal outcomes. MicroRNAs (miRNAs) have an increasing impact on the different pathways of viral infections. Within the transition process from acute phase to convalescence with 18 CCHF patients, we investigated the impacts on miRNA via microarray for the first time. We also compared miRNA gene expression in 16 severe and 15 mild cases. We identified Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathways associated with significant miRNAs utilizing DIANA TOOLS mirPath v.3. In this study, miR-15b-5p and miR-29a-3p were significantly downregulated in statistical terms; miR-4741, miR-937-5p, miR-6068, miR-7110-5p, miR-6126, and miR-7107-5p were upregulated in acute cases in comparison with convalescent patients (p ≤ .05). In total, 28 miRNAs (8 downregulated, 20 upregulated) were differentially expressed in severe CCHF patients as compared with mild cases (p ≤ .05). Whereas miR-6732-3p, miR-4436b-5p, miR-483-3p, and miR-6807-5p had the highest downregulation, miR-532-5p, miR-142-5p, miR-29c-3p, and let-7f-5p had the highest upregulation in severe patients in comparison with mild cases. Consequently, we determined that CCHF-induced miRNAs are associated with antiviral and proinflammatory pathways in acute and severe cases. In comparison with convalescence, these miRNAs in acute period may be therapeutic targets.
克里米亚刚果出血热(CCHF)是最重要的病毒感染之一,由克里米亚刚果出血热正布尼亚病毒(CCHFV)引起。CCHF的严重程度可从轻度非特异性疾病到具有致命后果的严重疾病不等。微小RNA(miRNA)对病毒感染的不同途径的影响日益增加。在18例CCHF患者从急性期到恢复期的过渡过程中,我们首次通过微阵列研究了对miRNA的影响。我们还比较了16例重症和15例轻症病例中的miRNA基因表达。我们利用DIANA TOOLS mirPath v.3鉴定了与显著miRNA相关的京都基因与基因组百科全书(KEGG)和基因本体论(GO)途径。在本研究中,miR-15b-5p和miR-29a-3p在统计学上显著下调;与恢复期患者相比,急性病例中miR-4741、miR-937-5p、miR-6068、miR-7110-5p、miR-6126和miR-7107-5p上调(p≤0.05)。与轻症病例相比,重症CCHF患者中共有28种miRNA(8种下调,20种上调)差异表达(p≤0.05)。与轻症病例相比,miR-6732-3p、miR-4436b-5p、miR-483-3p和miR-6807-5p下调幅度最大,而miR-532-5p、miR-142-5p、miR-29c-3p和let-7f-5p在重症患者中上调幅度最大。因此,我们确定CCHF诱导的miRNA在急性和重症病例中与抗病毒和促炎途径相关。与恢复期相比,急性期的这些miRNA可能是治疗靶点。