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

Autor:	Rawlinson SM; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.; Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Melbourne, Victoria, 3010, Australia., Zhao T; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.; Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Melbourne, Victoria, 3010, Australia., Rozario AM; School of Chemistry, Monash University, Clayton, Victoria, 3800, Australia., Rootes CL; CSIRO Health & Biosecurity, Australian Animal Health Laboratory, Geelong, Victoria, 3220, Australia., McMillan PJ; Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Melbourne, Victoria, 3010, Australia.; Biological Optical Microscopy Platform, The University of Melbourne, Parkville, Victoria, 3010, Australia., Purcell AW; Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia., Woon A; Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia., Marsh GA; CSIRO Health & Biosecurity, Australian Animal Health Laboratory, Geelong, Victoria, 3220, Australia., Lieu KG; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia., Wang LF; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, 169857, Singapore., Netter HJ; Victorian Infectious Diseases Reference Laboratory, Melbourne Health, The Peter Doherty Institute, Victoria, 3000, Australia., Bell TDM; School of Chemistry, Monash University, Clayton, Victoria, 3800, Australia., Stewart CR; CSIRO Health & Biosecurity, Australian Animal Health Laboratory, Geelong, Victoria, 3220, Australia., Moseley GW; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia. greg.moseley@monash.edu.; Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Melbourne, Victoria, 3010, Australia. greg.moseley@monash.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2018 Aug 03; Vol. 9 (1), pp. 3057. Date of Electronic Publication: 2018 Aug 03.
DOI:	10.1038/s41467-018-05354-7
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu