Micro RNAs of Epstein-Barr Virus Promote Cell Cycle Progression and Prevent Apoptosis of Primary Human B Cells

PLoS Pathogens

Andreas Moosmann¹  Wolfgang Hammerschmidt²  Eri Seto²  Nicole Walz³  Adam Grundhoff³  Sebastian Grömminger⁴ 

[1] Clinical Cooperation Group Molecular Oncology, Ludwig Maximilians-University Munich and Helmholtz Zentrum München, German Research Center for Environment and Health, Munich, Germany;Department of Gene Vectors, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany;Heinrich-Pette-Institute for Experimental Virology and Immunology, Hamburg, Germany;Institute for Clinical and Molecular Biology, Helmholtz Zentrum München, German Research Center for Environment and Health, Munich, Germany

关键词: MicroRNAs;    B cells;    Prototypes;    Cell cycle;    cell division;    Apoptosis;    Gene targeting;    Sequence alignment;    Genetic loci;   

DOI  :  10.1371/journal.ppat.1001063

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY