Buzdin Anton A, Artcibasova Alina V, Fedorova Natalya F, Suntsova Maria V, Garazha Andrew V, Sorokin Maxim I, Allina Daria, Shalatonin Mikhail, Borisov Nikolay M, Zhavoronkov Alex A, Kovalchuk Igor, Kovalchuk Olga, Kushch Alla A
a Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia.
b Group for Genomic Regulation of Cell Signaling Systems, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry , Moscow , Russia.
Cell Cycle. 2016 Dec 16;15(24):3378-3389. doi: 10.1080/15384101.2016.1241928.
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.
对人巨细胞病毒（HCMV）感染的反应在很大程度上是个体特异性和细胞类型特异性的。我们研究了两种人成纤维细胞原代细胞培养物中的分子谱，这两种培养物分别对HCMV感染高度敏感或敏感性较低。我们在感染的早期（3小时）阶段筛选了基因和微小RNA（miR）的表达。为了评估分子途径激活谱，我们应用了生物信息学算法OncoFinder和MiRImpact。在两种细胞类型中，mRNA和miR水平的途径调节特性明显不同。令人惊讶的是，与未感染的对照相比，在感染的高度敏感细胞中，我们观察到miR表达谱的“冻结”。我们的结果证明，在敏感细胞中，HCMV在感染的最早阶段就阻断了微小RNA表达的细胞内调节。这些数据提示了HCMV产物的一些新功能，并证明了miR表达停滞对宿主编码因子的依赖性。
