Global Reprogramming of Host SUMOylation during Influenza Virus Infection

Patricia Domingues, Filip Golebiowski, Michael H. Tatham, Antonio M. Lopes, Aislynn Taggart, Ronald T. Hay, Benjamin G. Hale (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    74 Citations (Scopus)
    227 Downloads (Pure)

    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.

    Original languageEnglish
    Pages (from-to)1467-1480
    Number of pages14
    JournalCell Reports
    Volume13
    Issue number7
    Early online date5 Nov 2015
    DOIs
    Publication statusPublished - 17 Nov 2015

    ASJC Scopus subject areas

    • General Biochemistry,Genetics and Molecular Biology

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