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Global Reprogramming of Host SUMOylation during Influenza Virus Infection


Domingues, P; Golebiowski, F; Tatham, M H; Lopes, A M; Taggart, A; Hay, R T; Hale, B G (2015). Global Reprogramming of Host SUMOylation during Influenza Virus Infection. Cell Reports, 13(7):1467-1480.

Abstract

Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here,we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome re-modeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection.

Abstract

Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here,we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome re-modeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:5 November 2015
Deposited On:15 Feb 2016 15:19
Last Modified:18 Apr 2018 11:47
Publisher:Cell Press (Elsevier)
ISSN:2211-1247
Funders:European Research Council (ERC) under EU FP7 ERC Starting Grant Agreement 335809 (SUMOFLU), MRC UK, and the European Commission under EU FP7 Marie Curie CIG 321703 (UBIFLU), Cancer Research UK programme grant (C434/A13067), Wellcome Trust Senior Investigator Award (098391/Z/12/Z)
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.celrep.2015.10.001
Official URL:http://www.cell.com/cell-reports/abstract/S2211-1247%2815%2901139-0
PubMed ID:26549460
Project Information:
  • : FunderFP7
  • : Grant ID335809
  • : Project TitleSUMOFLU - Interplay between influenza viruses and host SUMO pathways
  • : FunderFP7
  • : Grant ID321703
  • : Project TitleUBIFLU - Ubiquitin Signalling Pathways Required for Influenza Virus Replication: Biological Characterisation and Identification of Novel Drug Targets
  • : FunderFP7
  • : Grant ID
  • : Project TitleEuropean Research Council (ERC) under EU FP7 ERC Starting Grant Agreement 335809 (SUMOFLU)
  • : FunderFP7
  • : Grant ID
  • : Project TitleMRC UK, and the European Commission under EU FP7 Marie Curie CIG 321703 (UBIFLU)
  • : Funder
  • : Grant ID
  • : Project TitleCancer Research UK programme grant (C434/A13067)
  • : Funder
  • : Grant ID
  • : Project TitleWellcome Trust Senior Investigator Award (098391/Z/12/Z)

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