KAP1 Is a Host Restriction Factor That Promotes Human Adenovirus E1B-55K SUMO Modification.

Autor:	Bürck C; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany., Mund A; Chromatin Structure and Function Group, Protein Signaling Program, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Berscheminski J; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany., Kieweg L; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany., Müncheberg S; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany., Dobner T; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany thomas.dobner@hpi.uni-hamburg.de sabrina.schreiner@tum.de., Schreiner S; Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany thomas.dobner@hpi.uni-hamburg.de sabrina.schreiner@tum.de.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2015 Nov 04; Vol. 90 (2), pp. 930-46. Date of Electronic Publication: 2015 Nov 04 (Print Publication: 2016).
DOI:	10.1128/JVI.01836-15
Abstrakt:	Unlabelled: Once transported to the replication sites, human adenoviruses (HAdVs) need to ensure decondensation and transcriptional activation of their viral genomes to synthesize viral proteins and initiate steps to reprogram the host cell for viral replication. These early stages during adenoviral infection are poorly characterized but represent a decisive moment in the establishment of a productive infection. Here, we identify a novel host viral restriction factor, KAP1. This heterochromatin-associated transcription factor regulates the dynamic organization of the host chromatin structure via its ability to influence epigenetic marks and chromatin compaction. In response to DNA damage, KAP1 is phosphorylated and functionally inactive, resulting in chromatin relaxation. We discovered that KAP1 posttranslational modification is dramatically altered during HAdV infection to limit the antiviral capacity of this host restriction factor, which represents an essential step required for efficient viral replication. Conversely, we also observed during infection an HAdV-mediated decrease of KAP1 SUMO moieties, known to promote chromatin decondensation events. Based on our findings, we provide evidence that HAdV induces KAP1 deSUMOylation to minimize epigenetic gene silencing and to promote SUMO modification of E1B-55K by a so far unknown mechanism. Importance: Here we describe a novel cellular restriction factor for human adenovirus (HAdV) that sheds light on very early modulation processes in viral infection. We reported that chromatin formation and cellular SWI/SNF chromatin remodeling play key roles in HAdV transcriptional regulation. We observed that the cellular chromatin-associated factor and epigenetic reader SPOC1 represses HAdV infection and gene expression. Here, we illustrate the role of the SPOC1-interacting factor KAP1 during productive HAdV growth. KAP1 binds to the viral E1B-55K protein, promoting its SUMO modification, therefore illustrating a crucial step for efficient viral replication. Simultaneously, KAP1 posttranslational modification is dramatically altered during infection. We observed an HAdV-mediated decrease in KAP1 SUMOylation, known to promote chromatin decondensation events. These findings indicate that HAdV induces the loss of KAP1 SUMOylation to minimize epigenetic gene silencing and to promote the SUMO modification of E1B-55K by a so far unknown mechanism. (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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