Dysregulation of the cohesin subunit RAD21 by Hepatitis C virus mediates host-virus interactions.
Carrier Proteins
/ genetics
Cell Cycle Proteins
/ genetics
Cell Line, Tumor
Cell Nucleus
/ virology
Chromatin
/ genetics
Chromosomal Instability
/ genetics
Chromosomal Proteins, Non-Histone
/ genetics
Cytoplasm
/ virology
DNA-Binding Proteins
Hepacivirus
/ genetics
Hepatitis C
/ genetics
Hepatocytes
/ virology
Host-Pathogen Interactions
/ genetics
Humans
Mitosis
/ genetics
Nuclear Proteins
/ genetics
Phosphoproteins
/ genetics
Proto-Oncogene Proteins
/ genetics
Serine Proteases
/ genetics
Viral Nonstructural Proteins
/ genetics
Virus Replication
/ genetics
Cohesins
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 03 2019
18 03 2019
Historique:
accepted:
24
01
2019
revised:
30
12
2018
received:
02
05
2018
pubmed:
31
1
2019
medline:
16
10
2019
entrez:
31
1
2019
Statut:
ppublish
Résumé
Hepatitis C virus (HCV) infection is the leading cause of chronic hepatitis, which often results in liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCV possesses an RNA genome and its replication is confined to the cytoplasm. Yet, infection with HCV leads to global changes in gene expression, and chromosomal instability (CIN) in the host cell. The mechanisms by which the cytoplasmic virus affects these nuclear processes are elusive. Here, we show that HCV modulates the function of the Structural Maintenance of Chromosome (SMC) protein complex, cohesin, which tethers remote regions of chromatin. We demonstrate that infection of hepatoma cells with HCV leads to up regulation of the expression of the RAD21 cohesin subunit and changes cohesin residency on the chromatin. These changes regulate the expression of genes associated with virus-induced pathways. Furthermore, siRNA downregulation of viral-induced RAD21 reduces HCV infection. During mitosis, HCV infection induces hypercondensation of chromosomes and the appearance of multi-centrosomes. We provide evidence that the underlying mechanism involves the viral NS3/4 protease and the cohesin regulator, WAPL. Altogether, our results provide the first evidence that HCV induces changes in gene expression and chromosome structure of infected cells by modulating cohesin.
Identifiants
pubmed: 30698808
pii: 5304315
doi: 10.1093/nar/gkz052
pmc: PMC6412124
doi:
Substances chimiques
Carrier Proteins
0
Cell Cycle Proteins
0
Chromatin
0
Chromosomal Proteins, Non-Histone
0
DNA-Binding Proteins
0
Nuclear Proteins
0
Phosphoproteins
0
Proto-Oncogene Proteins
0
RAD21 protein, human
0
Viral Nonstructural Proteins
0
WAPL protein, human
0
NS3-4A serine protease, Hepatitis C virus
EC 3.4.-
Serine Proteases
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2455-2471Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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