title: Early stage of cytomegalovirus infection suppresses host microRNA expression regulation in human fibroblasts.
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.
authors.affiliation: 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.|c National Research Centre "Kurchatov Institute", Centre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies , Moscow , Russia.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Buzdin
authors.affiliation: a Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia.|d Pathway Pharmaceuticals , Wan Chai, Hong Kong , Hong Kong SAR.
authors.forename: Alina V
authors.initials: AV
authors.lastname: Artcibasova
authors.affiliation: e N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation , Moscow , Russia.
authors.forename: Natalya F
authors.initials: NF
authors.lastname: Fedorova
authors.affiliation: 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.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Suntsova
authors.affiliation: a Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia.|f Moscow Institute of Physics and Technology , Dolgoprudny, Moscow region , Russia.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Garazha
authors.affiliation: g First Oncology Research and Advisory Center , Moscow , Russia.
authors.forename: Maxim I
authors.initials: MI
authors.lastname: Sorokin
authors.affiliation: f Moscow Institute of Physics and Technology , Dolgoprudny, Moscow region , Russia.|g First Oncology Research and Advisory Center , Moscow , Russia.
authors.forename: Daria
authors.initials: D
authors.lastname: Allina
authors.affiliation: h The Morozov Children's City Hospital , Moscow Russia.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Shalatonin
authors.affiliation: c National Research Centre "Kurchatov Institute", Centre for Convergence of Nano-, Bio-, Information and Cognitive Sciences and Technologies , Moscow , Russia.|g First Oncology Research and Advisory Center , Moscow , Russia.
authors.forename: Nikolay M
authors.initials: NM
authors.lastname: Borisov
authors.affiliation: a Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia.|d Pathway Pharmaceuticals , Wan Chai, Hong Kong , Hong Kong SAR.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Zhavoronkov
authors.affiliation: i Department of Biological Sciences , University of Lethbridge , Lethbridge , AB , Canada.
authors.forename: Igor
authors.initials: I
authors.lastname: Kovalchuk
authors.affiliation: i Department of Biological Sciences , University of Lethbridge , Lethbridge , AB , Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
authors.affiliation: e N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation , Moscow , Russia.
authors.forename: Alla A
authors.initials: AA
authors.lastname: Kushch
mesh_terms: D000328:Adult; D002460:Cell Line; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D014764:Viral Proteins
keywords: Cytomegalovirus infection; gene transcription; human fibroblasts; intracellular signaling pathway regulation; microRNA; total miRNAome