The Antiresection Activity of the X Protein Encoded by Hepatitis Virus B

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Laifeng RenCong Liu

Abstract

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, CRL4WDR70 , through its H-box, we show that HBx inhibits H2B monoubiquitylation at lysine 120 at double-strand breaks, thus reducing the efficiency of long-range resection. We further show that directly impairing H2B monoubiquitylation elicited tumorigenesis upon ...Continue Reading

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Citations

Oct 22, 2019·Frontiers in Physiology·Shahd FouadVincenzo D'Angiolella
Feb 3, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Ming ZengCong Liu
May 14, 2021·Seminars in Liver Disease·Kazuma SekibaKazuhiko Koike
Sep 25, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Masataka Tsuge

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Methods Mentioned

BETA
immunoprecipitation
ChIP
transfection
PCR
xenograft
xenografts
Antiresection
biopsies
ubiquitination

Software Mentioned

GraphPad Prism

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