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] |
---|
Links: |
---|
Themen: |
Antiviral |
---|
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 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM36507019X | ||
003 | DE-627 | ||
005 | 20231227132121.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1073/pnas.2306390120 |2 doi | |
028 | 5 | 2 | |a pubmed24n1226.xml |
035 | |a (DE-627)NLM36507019X | ||
035 | |a (NLM)38015841 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Xia, Yuchen |e verfasserin |4 aut | |
245 | 1 | 0 | |a Nucleolin binds to and regulates transcription of hepatitis B virus covalently closed circular DNA minichromosome |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 30.11.2023 | ||
500 | |a Date Revised 13.12.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a HBV minichromosome | |
650 | 4 | |a antiviral | |
650 | 4 | |a epigenetics | |
650 | 4 | |a proteomics | |
650 | 4 | |a viral replication | |
650 | 7 | |a DNA, Viral |2 NLM | |
650 | 7 | |a DNA, Circular |2 NLM | |
700 | 1 | |a Cheng, Xiaoming |e verfasserin |4 aut | |
700 | 1 | |a Nilsson, Tobias |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Min |e verfasserin |4 aut | |
700 | 1 | |a Zhao, Gaihong |e verfasserin |4 aut | |
700 | 1 | |a Inuzuka, Tadashi |e verfasserin |4 aut | |
700 | 1 | |a Teng, Yan |e verfasserin |4 aut | |
700 | 1 | |a Li, Yao |e verfasserin |4 aut | |
700 | 1 | |a Anderson, D Eric |e verfasserin |4 aut | |
700 | 1 | |a Holdorf, Meghan |e verfasserin |4 aut | |
700 | 1 | |a Liang, T Jake |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Proceedings of the National Academy of Sciences of the United States of America |d 1915 |g 120(2023), 49 vom: 05. Dez., Seite e2306390120 |w (DE-627)NLM000008982 |x 1091-6490 |7 nnns |
773 | 1 | 8 | |g volume:120 |g year:2023 |g number:49 |g day:05 |g month:12 |g pages:e2306390120 |
856 | 4 | 0 | |u http://dx.doi.org/10.1073/pnas.2306390120 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 120 |j 2023 |e 49 |b 05 |c 12 |h e2306390120 |