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Early stage of cytomegalovirus infection suppresses host microRNA expression regulation in human fibroblasts
Authors:Anton A. Buzdin  Alina V. Artcibasova  Natalya F. Fedorova  Maria V. Suntsova  Andrew V. Garazha  Maxim I. Sorokin
Affiliation:1. Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia;2. Group for Genomic Regulation of Cell Signaling Systems, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia;3. National Research Centre “Kurchatov Institute”, Centre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies, Moscow, Russia;4. Pathway Pharmaceuticals, Wan Chai, Hong Kong, Hong Kong SAR;5. N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation, Moscow, Russia;6. Moscow Institute of Physics and Technology, Dolgoprudny, Moscow region, Russia;7. First Oncology Research and Advisory Center, Moscow, Russia
Abstract:
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.
Keywords:
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