title: Global Reprogramming of Host SUMOylation during Influenza Virus 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 remodeling. 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.
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Domingues
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, UK.
authors.forename: Filip
authors.initials: F
authors.lastname: Golebiowski
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Tatham
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, UK.
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Lopes
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, UK.
authors.forename: Aislynn
authors.initials: A
authors.lastname: Taggart
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Hay
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Garscube Campus, 464 Bearsden Road, Glasgow G61 1QH, UK. Electronic address: hale.ben@virology.uzh.ch.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Hale
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004285:Dogs; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D061985:Madin Darby Canine Kidney Cells; D021381:Protein Transport; D020543:Proteome / Q000378:metabolism; D012367:RNA, Viral / Q000502:physiology; D058207:Sumoylation; D015533:Transcriptional Activation; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014709:Vero Cells
chemical_list: C454900:CDC73 protein, human; D020543:Proteome; D012367:RNA, Viral; D025521:Tumor Suppressor Proteins