Anton A Buzdin, Alina V Artcibasova, Natalya F Fedorova, Maria V Suntsova, Andrew V Garazha, Maxim I Sorokin, Daria Allina, Mikhail Shalatonin, Nikolay M Borisov, Alex A Zhavoronkov, Igor Kovalchuk, Olga Kovalchuk, Alla A Kushch
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引用次数: 0
摘要
人类巨细胞病毒(HCMV)感染反应在很大程度上具有个体和细胞类型特异性。我们研究了人类成纤维细胞的两种原代细胞培养物的分子特征,这两种细胞分别对 HCMV 感染高度敏感或略微敏感。我们筛选了感染早期(3 小时)的基因和 microRNA(miRs)表达。为了评估分子通路激活情况,我们应用了生物信息学算法 OncoFinder 和 MiRImpact。在这两种细胞类型中,mRNA 和 miR 水平的通路调控特性明显不同。令人惊讶的是,在受感染的高度敏感细胞中,我们观察到 miR 表达谱与未感染对照组相比出现了 "冻结"。我们的结果证明,在敏感细胞中,HCMV 在感染的最初阶段就已经阻断了细胞内对 microRNA 表达的调控。这些数据提示了 HCMV 产物的一些新功能,并证明了 miR 表达受阻取决于宿主编码的因子。
Early stage of cytomegalovirus infection suppresses host microRNA expression regulation in human fibroblasts.
Responses to human cytomegalovirus (HCMV) infection are largely individual and cell type specific. We investigated molecular profiles in 2 primary cell cultures of human fibroblasts, which are highly or marginally sensitive to HCMV infection, respectively. We screened expression of genes and microRNAs (miRs) at the early (3 hours) stage of infection. To assess molecular pathway activation profiles, we applied bioinformatic algorithms OncoFinder and MiRImpact. In both cell types, pathway regulation properties at mRNA and miR levels were markedly different. Surprisingly, in the infected highly sensitive cells, we observed a "freeze" of miR expression profiles compared to uninfected controls. Our results evidence that in the sensitive cells, HCMV blocks intracellular regulation of microRNA expression already at the earliest stage of infection. These data suggest somewhat new functions for HCMV products and demonstrate dependence of miR expression arrest on the host-encoded factors.