Global reprogramming of host SUMOylation during influenza virus infection

Domingues, P., Golebiowski, F., Tatham, M. H., Lopes, A. M., Taggart, A., Hay, R. T. and Hale, B. G. (2015) Global reprogramming of host SUMOylation during influenza virus infection. Cell Reports, 13(7), pp. 1467-1480. (doi: 10.1016/j.celrep.2015.10.001) (PMID:26549460) (PMCID:PMC4660286)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Golebiowski, Dr Filip and Taggart, Ms Aislynn and Hale, Dr Benjamin
Authors: Domingues, P., Golebiowski, F., Tatham, M. H., Lopes, A. M., Taggart, A., Hay, R. T., and Hale, B. G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cell Reports
Publisher:Elsevier
ISSN:2211-1247
ISSN (Online):2211-1247
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Cell Reports 13(17):1467-1480
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
604512UBIFLU: Ubiquitin Signalling Pathways Required for Influenza Virus Replication: Biological Characterisation and Identification of Novel Drug TargetsBenjamin HaleWellcome Trust (WELLCOME)UNSPECIFIEDMVLS III - CENTRE FOR VIRUS RESEARCH