Sp100 isoform-specific regulation of human adenovirus 5 gene expression

Julia Berscheminski, Peter Wimmer, Juliane Brun, Wing Hang Ip, Peter Groitl, Tim Horlacher, Ellis Jaffray, Ron T. Hay, Thomas Dobner (Lead / Corresponding author), Sabrina Schreiner

    Research output: Contribution to journalArticlepeer-review

    28 Citations (Scopus)

    Abstract

    Promyelocytic leukemia nuclear bodies (PML-NBs) are nuclear structures that accumulate intrinsic host factors to restrict viral infections. To ensure viral replication, these must be limited by expression of viral early regulatory proteins that functionally inhibit PML-NB-associated antiviral effects. To benefit from the activating capabilities of Sp100A and simultaneously limit repression by Sp100B, -C, and -HMG, adenoviruses (Ads) employ several features to selectively and individually target these isoforms. Ads induce relocalization of Sp100B, -C, and -HMG from PML-NBs prior to association with viral replication centers. In contrast, Sp100A is kept at the PML tracks that surround the newly formed viral replication centers as designated sites of active transcription. We concluded that the host restriction factors Sp100B, -C, and -HMG are potentially inactivated by active displacement from these sites, whereas Sp100A is retained to amplify Ad gene expression. Ad-dependent loss of Sp100 SUMOylation is another crucial part of the virus repertoire to counteract intrinsic immunity by circumventing Sp100 association with HP1, therefore limiting chromatin condensation. We provide evidence that Ad selectively counteracts antiviral responses and, at the same time, benefits from PML-NB-associated components which support viral gene expression by actively recruiting them to PML track-like structures. Our findings provide insights into novel strategies for manipulating transcriptional regulation to either inactivate or amplify viral gene expression.
    Original languageEnglish
    Pages (from-to)6076-6092
    Number of pages17
    JournalJournal of Virology
    Volume88
    Issue number11
    DOIs
    Publication statusPublished - Jun 2014

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