St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

Viral DNA binding protein SUMOylation promotes PML nuclear body localization next to viral replication centers

Thumbnail
View/Open
Paulus_2020_mBio_ViralDNA_VoR_CCBY.pdf (2.643Mb)
Date
03/2020
Author
Stubbe, Miona
Mai, Julia
Paulus, Christina
Stubbe, Hans Christian
Berscheminski, Julia
Karimi, Maryam
Hofmann, Samuel
Weber, Elisabeth
Hadian, Kamyar
Hay, Ron
Groitl, Peter
Nevels, Michael
Dobner, Thomas
Schreiner, Sabrina
Keywords
DNA binding protein
E2A/DBP
HAdV
Human adenovirus
PML-NB
Replication centers
Sp100
SUMO
Transcription
Virus
QH301 Biology
QR355 Virology
Microbiology
Virology
DAS
Metadata
Show full item record
Abstract
Human adenoviruses (HAdVs) have developed mechanisms to manipulate cellular antiviral measures to ensure proper DNA replication, with detailed processes far from being understood. Host cells repress incoming viral genomes through a network of transcriptional regulators that normally control cellular homeostasis. The nuclear domains involved are promyelocytic leukemia protein nuclear bodies (PML-NBs), interferon-inducible, dot-like nuclear structures and hot spots of SUMO posttranslational modification (PTM). In HAdV-infected cells, such SUMO factories are found in close proximity to newly established viral replication centers (RCs) marked by the adenoviral DNA binding protein (DBP) E2A. Here, we show that E2A is a novel target of host SUMOylation, leading to PTMs supporting E2A function in promoting productive infection. Our data show that SUMOylated E2A interacts with PML. Decreasing SUMO-E2A protein levels by generating HAdV variants mutated in the three main SUMO conjugation motifs (SCMs) led to lower numbers of viral RCs and PML-NBs, and these two structures were no longer next to each other. Our data further indicate that SUMOylated E2A binds the host transcription factor Sp100A, promoting HAdV gene expression, and represents the molecular bridge between PML tracks and adjacent viral RCs. Consequently, E2A SCM mutations repressed late viral gene expression and progeny production. These data highlight a novel mechanism used by the virus to benefit from host antiviral responses by exploiting the cellular SUMO conjugation machinery.
Citation
Stubbe , M , Mai , J , Paulus , C , Stubbe , H C , Berscheminski , J , Karimi , M , Hofmann , S , Weber , E , Hadian , K , Hay , R , Groitl , P , Nevels , M , Dobner , T & Schreiner , S 2020 , ' Viral DNA binding protein SUMOylation promotes PML nuclear body localization next to viral replication centers ' , mBio , vol. 11 , no. 2 , e00049-20 . https://doi.org/10.1128/mBio.00049-20
Publication
mBio
Status
Peer reviewed
DOI
https://doi.org/10.1128/mBio.00049-20
ISSN
2150-7511
Type
Journal article
Rights
Copyright © 2020 Stubbe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Description
We thank Kenji Schorpp (Munich, Germany) for support with our yeast work and Roger Everett (Glasgow, United Kingdom) for reagents. We greatly appreciate the scientific discussion with Michelle Vincendeau, Ruth Brack-Werner, and Ulrike Protzer. This work was supported by the Dräger Stiftung eV, the Deutsche Krebshilfe eV, and the Deutsche Forschungsgemeinschaft (DFG TRR179 P16).
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/19747

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter