Nucleolin binds to and regulates transcription of hepatitis B virus covalently closed circular DNA minichromosome

Hepatitis B virus (HBV) remains a major public health threat with nearly 300 million people chronically infected worldwide who are at a high risk of developing hepatocellular carcinoma. Current therapies are effective in suppressing HBV replication but rarely lead to cure. Current therapies do not affect the HBV covalently closed circular DNA (cccDNA), which serves as the template for viral transcription and replication and is highly stable in infected cells to ensure viral persistence. In this study, we aim to identify and elucidate the functional role of cccDNA-associated host factors using affinity purification and protein mass spectrometry in HBV-infected cells. Nucleolin was identified as a key cccDNA-binding protein and shown to play an important role in HBV cccDNA transcription, likely via epigenetic regulation. Targeting nucleolin to silence cccDNA transcription in infected hepatocytes may be a promising therapeutic strategy for a functional cure of HBV.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:120

Enthalten in:

Proceedings of the National Academy of Sciences of the United States of America - 120(2023), 49 vom: 05. Dez., Seite e2306390120

Sprache:

Englisch

Beteiligte Personen:

Xia, Yuchen [VerfasserIn]
Cheng, Xiaoming [VerfasserIn]
Nilsson, Tobias [VerfasserIn]
Zhang, Min [VerfasserIn]
Zhao, Gaihong [VerfasserIn]
Inuzuka, Tadashi [VerfasserIn]
Teng, Yan [VerfasserIn]
Li, Yao [VerfasserIn]
Anderson, D Eric [VerfasserIn]
Holdorf, Meghan [VerfasserIn]
Liang, T Jake [VerfasserIn]

Links:

Volltext

Themen:

Antiviral
DNA, Circular
DNA, Viral
Epigenetics
HBV minichromosome
Journal Article
Proteomics
Viral replication

Anmerkungen:

Date Completed 30.11.2023

Date Revised 13.12.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1073/pnas.2306390120

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM36507019X