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Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response

Author

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  • Stephen M. Rawlinson

    (Biomedicine Discovery Institute, Monash University, Clayton
    Bio21 Institute, The University of Melbourne, Melbourne)

  • Tianyue Zhao

    (Biomedicine Discovery Institute, Monash University, Clayton
    Bio21 Institute, The University of Melbourne, Melbourne)

  • Ashley M. Rozario

    (School of Chemistry, Monash University, Clayton)

  • Christina L. Rootes

    (Australian Animal Health Laboratory, Geelong)

  • Paul J. McMillan

    (Bio21 Institute, The University of Melbourne, Melbourne
    The University of Melbourne, Parkville)

  • Anthony W. Purcell

    (Biomedicine Discovery Institute, Monash University, Clayton
    Monash University, Clayton)

  • Amanda Woon

    (Biomedicine Discovery Institute, Monash University, Clayton
    Monash University, Clayton)

  • Glenn A. Marsh

    (Australian Animal Health Laboratory, Geelong)

  • Kim G. Lieu

    (Biomedicine Discovery Institute, Monash University, Clayton)

  • Lin-Fa Wang

    (Programme in Emerging Infectious Diseases, Duke-NUS Medical School)

  • Hans J. Netter

    (Melbourne Health, The Peter Doherty Institute)

  • Toby D. M. Bell

    (School of Chemistry, Monash University, Clayton)

  • Cameron R. Stewart

    (Australian Animal Health Laboratory, Geelong)

  • Gregory W. Moseley

    (Biomedicine Discovery Institute, Monash University, Clayton
    Bio21 Institute, The University of Melbourne, Melbourne)

Abstract

Recent studies indicate that nucleoli play critical roles in the DNA-damage response (DDR) via interaction of DDR machinery including NBS1 with nucleolar Treacle protein, a key mediator of ribosomal RNA (rRNA) transcription and processing. Here, using proteomics, confocal and single molecule super-resolution imaging, and infection under biosafety level-4 containment, we show that this nucleolar DDR pathway is targeted by infectious pathogens. We find that the matrix proteins of Hendra virus and Nipah virus, highly pathogenic viruses of the Henipavirus genus in the order Mononegavirales, interact with Treacle and inhibit its function, thereby silencing rRNA biogenesis, consistent with mimicking NBS1–Treacle interaction during a DDR. Furthermore, inhibition of Treacle expression/function enhances henipavirus production. These data identify a mechanism for viral modulation of host cells by appropriating the nucleolar DDR and represent, to our knowledge, the first direct intranucleolar function for proteins of any mononegavirus.

Suggested Citation

  • Stephen M. Rawlinson & Tianyue Zhao & Ashley M. Rozario & Christina L. Rootes & Paul J. McMillan & Anthony W. Purcell & Amanda Woon & Glenn A. Marsh & Kim G. Lieu & Lin-Fa Wang & Hans J. Netter & Toby, 2018. "Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05354-7
    DOI: 10.1038/s41467-018-05354-7
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