PLoS Pathogens | |
Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication | |
Karita Peltonen1  Marikki Laiho1  Jussi Taipale2  Ilkka Julkunen3  Mikko Turunen4  Sampsa Hautaniemi4  Päivi M. Ojala5  Lauri Lyly5  Olli Kallioniemi6  Oxana Denisova6  Denis Kainov6  Johanna Viiliäinen7  Grzegorz Sarek7  Pirita Pekkonen7  Krista Ojala7  Raquel Diaz7  Markku Varjosalo7  Mari Teesalu7  Giuseppe Balistreri7  Juha Rantala8  | |
[1] Centre for Drug Discovery, University of Helsinki, Helsinki, Finland;Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America;Department of Virology, University of Turku and National Institute for Health and Welfare, Turku, Finland;Genome-Scale Biology Program, Research Programs Unit and Department of Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland;Genome-Scale Biology Program, Research Programs Unit, University of Helsinki, Biomedicum Helsinki, Helsinki, Finland;Institute for Molecular Medicine (FIMM), University of Helsinki, Biomedicum Helsinki, Helsinki, Finland;Translational Cancer Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland;VTT Medical Biotechnology, Turku, Finland | |
关键词: Viral replication; Fluorescence imaging; Cell cycle; cell division; Small interfering RNAs; Gene expression; Image analysis; DNA damage; Immunofluorescence; | |
DOI : 10.1371/journal.ppat.1005424 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
Kaposi’s sarcoma herpesvirus (KSHV) causes Kaposi’s sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored efficient activation of the viral lytic transcription program and viral reactivation. During lytic replication cells activated a p53 response, accumulated DNA damage and arrested at G2-phase. Depletion of p21, a p53 target gene, restored cell cycle progression and thereby impaired the virus reactivation cascade delaying the onset of virus replication induced cytopathic effect. Herpesviruses are known to reactivate in response to different kinds of stress, and our study now highlights the molecular events in the stressed host cell that KSHV has evolved to utilize to ensure efficient viral lytic replication.
【 授权许可】
CC BY
【 预 览 】
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RO201902016302086ZK.pdf | 6163KB | download |