SUMO Modification of Hepatitis B Virus Core Mediates Nuclear Entry, Promyelocytic Leukemia Nuclear Body Association, and Efficient Formation of Covalently Closed Circular DNA.


Journal

Microbiology spectrum
ISSN: 2165-0497
Titre abrégé: Microbiol Spectr
Pays: United States
ID NLM: 101634614

Informations de publication

Date de publication:
15 06 2023
Historique:
medline: 19 6 2023
pubmed: 18 5 2023
entrez: 18 5 2023
Statut: ppublish

Résumé

Persistence of hepatitis B virus (HBV) infection is due to a nuclear covalently closed circular DNA (cccDNA), generated from the virion-borne relaxed circular DNA (rcDNA) genome in a process likely involving numerous cell factors from the host DNA damage response (DDR). The HBV core protein mediates rcDNA transport to the nucleus and likely affects stability and transcriptional activity of cccDNA. Our study aimed at investigating the role of HBV core protein and its posttranslational modification (PTM) with SUMO (small ubiquitin-like modifiers) during the establishment of cccDNA. HBV core protein SUMO PTM was analyzed in His-SUMO-overexpressing cell lines. The impact of HBV core SUMOylation on association with cellular interaction partners and on the HBV life cycle was determined using SUMOylation-deficient mutants of the HBV core protein. Here, we show that the HBV core protein is posttranslationally modified by the addition of SUMO and that this modification impacts nuclear import of rcDNA. By using SUMOylation-deficient HBV core mutants, we show that SUMO modification is a prerequisite for the association with specific promyelocytic leukemia nuclear bodies (PML-NBs) and regulates the conversion of rcDNA to cccDNA. By

Identifiants

pubmed: 37199632
doi: 10.1128/spectrum.00446-23
pmc: PMC10269885
doi:

Substances chimiques

DNA, Circular 0
DNA, Viral 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0044623

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Samuel Hofmann (S)

Institute of Virology, School of Medicine, Technical University of Munich, Germany.
Institute of Virology, Hannover Medical School, Hannover, Germany.

Verena Plank (V)

Institute of Virology, School of Medicine, Technical University of Munich, Germany.

Peter Groitl (P)

Institute of Virology, School of Medicine, Technical University of Munich, Germany.

Nathalie Skvorc (N)

Institute of Virology, School of Medicine, Technical University of Munich, Germany.

Katharina Hofmann (K)

Institute of Virology, School of Medicine, Technical University of Munich, Germany.
Institute of Virology, Hannover Medical School, Hannover, Germany.

Julius Luther (J)

Institute of Virology, Hannover Medical School, Hannover, Germany.

Chunkyu Ko (C)

Institute of Virology, School of Medicine, Technical University of Munich, Germany.
Institute of Virology, Helmholtz Zentrum München, Munich, Germany.

Peter Zimmerman (P)

Department of Internal Medicine II/Molecular Biology, University Hospital Freiburg, Freiburg, Germany.

Volker Bruss (V)

Institute of Virology, Helmholtz Zentrum München, Munich, Germany.

Daniela Stadler (D)

Institute of Virology, School of Medicine, Technical University of Munich, Germany.
Institute of Virology, Helmholtz Zentrum München, Munich, Germany.

Arnaud Carpentier (A)

Institute of Experimental Virology, Twincore, Hannover, Germany.

Shahinda Rezk (S)

Institute of Virology, School of Medicine, Technical University of Munich, Germany.
Medical Research Institute, Department of Molecular and Diagnostic Microbiology, Alexandria University, Alexandria, Egypt.

Michael Nassal (M)

Department of Internal Medicine II/Molecular Biology, University Hospital Freiburg, Freiburg, Germany.

Ulrike Protzer (U)

Institute of Virology, School of Medicine, Technical University of Munich, Germany.
Institute of Virology, Helmholtz Zentrum München, Munich, Germany.
German Center for Infection Research, Munich, Germany.

Sabrina Schreiner (S)

Institute of Virology, School of Medicine, Technical University of Munich, Germany.
Institute of Virology, Hannover Medical School, Hannover, Germany.
Institute of Virology, Helmholtz Zentrum München, Munich, Germany.
German Center for Infection Research, Munich, Germany.
Cluster of Excellence RESIST (Resolving Infection Susceptibility; EXC 2155), Hannover Medical School, Hannover, Germany.

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