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Cell Rep. 2015 Nov 4. pii: S2211-1247(15)01139-0. doi: 10.1016/j.celrep.2015.10.001. [Epub ahead of print]
Global Reprogramming of Host SUMOylation during Influenza Virus Infection.
Domingues P1, Golebiowski F1, Tatham MH2, Lopes AM1, Taggart A1, Hay RT2, Hale BG3.
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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.
Copyright ? 2015 The Authors. Published by Elsevier Inc. All rights reserved.
PMID: 26549460 [PubMed - as supplied by publisher] Free full text
Global Reprogramming of Host SUMOylation during Influenza Virus Infection.
Domingues P1, Golebiowski F1, Tatham MH2, Lopes AM1, Taggart A1, Hay RT2, Hale BG3.
Author information
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.
Copyright ? 2015 The Authors. Published by Elsevier Inc. All rights reserved.
PMID: 26549460 [PubMed - as supplied by publisher] Free full text