The Antiresection Activity of the X Protein Encoded by Hepatitis Virus B.
Animals
Carcinoma, Hepatocellular
/ genetics
Cells, Cultured
DNA-Binding Proteins
/ genetics
Epigenesis, Genetic
Genomic Instability
/ genetics
Hepatitis B
/ genetics
Hepatitis B virus
/ genetics
Hepatocytes
/ cytology
Humans
Lithostathine
/ genetics
Liver Neoplasms
/ genetics
Mice
Sensitivity and Specificity
Trans-Activators
/ genetics
Viral Regulatory and Accessory Proteins
Virus Replication
/ genetics
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
28
08
2018
accepted:
11
02
2019
pubmed:
23
2
2019
medline:
17
6
2020
entrez:
22
2
2019
Statut:
ppublish
Résumé
Chronic infection of hepatitis B virus (HBV) is associated with an increased incidence of hepatocellular carcinoma (HCC). HBV encodes an oncoprotein, hepatitis B x protein (HBx), that is crucial for viral replication and interferes with multiple cellular activities including gene expression, histone modifications, and genomic stability. To date, it remains unclear how disruption of these activities contributes to hepatocarcinogenesis. Here, we report that HBV exhibits antiresection activity by disrupting DNA end resection, thus impairing the initial steps of homologous recombination (HR). This antiresection activity occurs in primary human hepatocytes undergoing a natural viral infection-replication cycle as well as in cells with integrated HBV genomes. Among the seven HBV-encoded proteins, we identified HBx as the sole viral factor that inhibits resection. By disrupting an evolutionarily conserved Cullin4A-damage-specific DNA binding protein 1-RING type of E3 ligase, CRL4
Identifiants
pubmed: 30791110
doi: 10.1002/hep.30571
pmc: PMC6618260
doi:
Substances chimiques
DNA-Binding Proteins
0
Lithostathine
0
REG1A protein, human
0
Trans-Activators
0
Viral Regulatory and Accessory Proteins
0
hepatitis B virus X protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2546-2561Subventions
Organisme : Ministry of Science and Technology of the People's Republic of China
ID : 2013CB911000
Pays : International
Organisme : Department of Science and Technology of Shanxi Province
ID : 201703D321013
Pays : International
Organisme : Department of Science and Technology of Sichuan Province
ID : 2017FZ0034
Pays : International
Organisme : National Natural Science Foundation of China
ID : 31471276
Pays : International
Organisme : National Natural Science Foundation of China
ID : 31771580
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81702795
Pays : International
Organisme : National Natural Science Foundation of China
ID : 81630038
Pays : International
Organisme : National Natural Science Foundation of China
ID : 8133001
Pays : International
Informations de copyright
© 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.
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