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Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication
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نویسنده
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balistreri g. ,viiliäinen j. ,turunen m. ,diaz r. ,lyly l. ,pekkonen p. ,rantala j. ,ojala k. ,sarek g. ,teesalu m. ,denisova o. ,peltonen k. ,julkunen i. ,varjosalo m. ,kainov d. ,kallioniemi o. ,laiho m. ,taipale j. ,hautaniemi s. ,ojala p.m.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 2
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چکیده
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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. © 2016 balistreri et al.
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آدرس
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university of helsinki,helsinki, Finland, university of helsinki,helsinki, Finland, department of pathology,haartman institute,university of helsinki,helsinki, Finland, university of helsinki,helsinki, Finland, university of helsinki,biomedicum helsinki,helsinki, Finland, university of helsinki,helsinki, Finland, vtt medical biotechnology,turku, Finland, university of helsinki,helsinki, Finland, university of helsinki,helsinki,finland,london research institute,cancer research uk,clare hall laboratories,south mimms, United Kingdom, university of helsinki,helsinki, Finland, institute for molecular medicine (fimm),university of helsinki,biomedicum helsinki,helsinki, Finland, centre for drug discovery,university of helsinki,helsinki, Finland, department of virology,university of turku and national institute for health and welfare,turku, Finland, university of helsinki,helsinki, Finland, institute for molecular medicine (fimm),university of helsinki,biomedicum helsinki,helsinki, Finland, institute for molecular medicine (fimm),university of helsinki,biomedicum helsinki,helsinki, Finland, centre for drug discovery,university of helsinki,helsinki,finland,department of radiation oncology,the johns hopkins university school of medicine,baltimore,md, United States, department of pathology,haartman institute,university of helsinki,helsinki, Finland, university of helsinki,biomedicum helsinki,helsinki, Finland, university of helsinki,helsinki,finland,foundation for the finnish cancer institute,helsinki,finland,section of virology,division of infectious diseases,department of medicine,imperial college london,london, United Kingdom
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Authors
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