SUMO Modification of Hepatitis B Virus Core Mediates Nuclear Entry, Promyelocytic Leukemia Nuclear Body Association, and Efficient Formation of Covalently Closed Circular DNA.
HBV
HBV core protein
PML-NBs
SUMO
chronic infection
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
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
e0044623Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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