title: Micro RNAs of Epstein-Barr virus promote cell cycle progression and prevent apoptosis of primary human B cells.
abstract: Cellular and viral microRNAs (miRNAs) are involved in many different processes of key importance and more than 10,000 miRNAs have been identified so far. In general, relatively little is known about their biological functions in mammalian cells because their phenotypic effects are often mild and many of their targets still await identification. The recent discovery that Epstein-Barr virus (EBV) and other herpesviruses produce their own, barely conserved sets of miRNAs suggests that these viruses usurp the host RNA silencing machinery to their advantage in contrast to the antiviral roles of RNA silencing in plants and insects. We have systematically introduced mutations in EBV's precursor miRNA transcripts to prevent their subsequent processing into mature viral miRNAs. Phenotypic analyses of these mutant derivatives of EBV revealed that the viral miRNAs of the BHRF1 locus inhibit apoptosis and favor cell cycle progression and proliferation during the early phase of infected human primary B cells. Our findings also indicate that EBV's miRNAs are not needed to control the exit from latency. The phenotypes of viral miRNAs uncovered by this genetic analysis indicate that they contribute to EBV-associated cellular transformation rather than regulate viral genes of EBV's lytic phase.
authors.affiliation: Department of Gene Vectors, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.
authors.forename: Eri
authors.initials: E
authors.lastname: Seto
authors.forename: Andreas
authors.initials: A
authors.lastname: Moosmann
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grömminger
authors.forename: Nicole
authors.initials: N
authors.lastname: Walz
authors.forename: Adam
authors.initials: A
authors.lastname: Grundhoff
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hammerschmidt
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology*; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D002472:Cell Transformation, Viral / Q000235:genetics*; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000821:virology; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000235:genetics*; D017735:Virus Latency / Q000235:genetics
chemical_list: C083278:BHRF1 protein, Human herpesvirus 4; D035683:MicroRNAs; D012367:RNA, Viral; D014764:Viral Proteins
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