Epigenetic silencing of antiviral genes renders clones of Huh-7 cells permissive for hepatitis C virus replication

Qiuyue Chen, Bray Denard, Hua Huang, Jin Ye

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) does not replicate efficiently in wild-type human hepatoma Huh-7 cells, but it replicates robustly in certain subclones of Huh-7 cells. Previously, we demonstrated that silencing of cyclic AMP (cAMP) response element binding protein 3-like 1 (CREB3L1), a cellular transcription factor that inhibits HCV replication, allows HCV to replicate in HRP1 cells, a subclone of Huh-7 cells permissive for HCV replication. Here we show that silencing of myxovirus resistant 1 (MX1), a known interferon-induced antiviral gene, is responsible for HRP4 cells, another subclone of Huh-7 cells, being permissive for HCV replication. Both CREB3L1 and MX1 are epigenetically silenced through DNA methylation in HRP1 and HRP4 cells, respectively. We further demonstrate that Huh-7 cells exist as a mixed population of cells with distinct patterns of gene methylation and HCV replicates in subpopulations of Huh-7 cells that have antiviral genes epigenetically silenced by DNA hypermethylation. Our results demonstrate that understanding the mechanism through which subclones of Huh-7 cells become permissive for HCV replication is crucial for studying their interaction with HCV.

Original languageEnglish (US)
Pages (from-to)659-665
Number of pages7
JournalJournal of Virology
Volume87
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Hepatitis C virus
Gene Silencing
Virus Replication
virus replication
Epigenomics
epigenetics
Hepacivirus
Antiviral Agents
Clone Cells
clones
genes
cells
Cyclic AMP Response Element-Binding Protein
response elements
Orthomyxoviridae
binding proteins
Genes
cyclic AMP
DNA methylation
DNA Methylation

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Epigenetic silencing of antiviral genes renders clones of Huh-7 cells permissive for hepatitis C virus replication. / Chen, Qiuyue; Denard, Bray; Huang, Hua; Ye, Jin.

In: Journal of Virology, Vol. 87, No. 1, 01.2013, p. 659-665.

Research output: Contribution to journalArticle

@article{18037b75b9ae4642af79bfac2e6d435a,
title = "Epigenetic silencing of antiviral genes renders clones of Huh-7 cells permissive for hepatitis C virus replication",
abstract = "Hepatitis C virus (HCV) does not replicate efficiently in wild-type human hepatoma Huh-7 cells, but it replicates robustly in certain subclones of Huh-7 cells. Previously, we demonstrated that silencing of cyclic AMP (cAMP) response element binding protein 3-like 1 (CREB3L1), a cellular transcription factor that inhibits HCV replication, allows HCV to replicate in HRP1 cells, a subclone of Huh-7 cells permissive for HCV replication. Here we show that silencing of myxovirus resistant 1 (MX1), a known interferon-induced antiviral gene, is responsible for HRP4 cells, another subclone of Huh-7 cells, being permissive for HCV replication. Both CREB3L1 and MX1 are epigenetically silenced through DNA methylation in HRP1 and HRP4 cells, respectively. We further demonstrate that Huh-7 cells exist as a mixed population of cells with distinct patterns of gene methylation and HCV replicates in subpopulations of Huh-7 cells that have antiviral genes epigenetically silenced by DNA hypermethylation. Our results demonstrate that understanding the mechanism through which subclones of Huh-7 cells become permissive for HCV replication is crucial for studying their interaction with HCV.",
author = "Qiuyue Chen and Bray Denard and Hua Huang and Jin Ye",
year = "2013",
month = "1",
doi = "10.1128/JVI.01984-12",
language = "English (US)",
volume = "87",
pages = "659--665",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "1",

}

TY - JOUR

T1 - Epigenetic silencing of antiviral genes renders clones of Huh-7 cells permissive for hepatitis C virus replication

AU - Chen, Qiuyue

AU - Denard, Bray

AU - Huang, Hua

AU - Ye, Jin

PY - 2013/1

Y1 - 2013/1

N2 - Hepatitis C virus (HCV) does not replicate efficiently in wild-type human hepatoma Huh-7 cells, but it replicates robustly in certain subclones of Huh-7 cells. Previously, we demonstrated that silencing of cyclic AMP (cAMP) response element binding protein 3-like 1 (CREB3L1), a cellular transcription factor that inhibits HCV replication, allows HCV to replicate in HRP1 cells, a subclone of Huh-7 cells permissive for HCV replication. Here we show that silencing of myxovirus resistant 1 (MX1), a known interferon-induced antiviral gene, is responsible for HRP4 cells, another subclone of Huh-7 cells, being permissive for HCV replication. Both CREB3L1 and MX1 are epigenetically silenced through DNA methylation in HRP1 and HRP4 cells, respectively. We further demonstrate that Huh-7 cells exist as a mixed population of cells with distinct patterns of gene methylation and HCV replicates in subpopulations of Huh-7 cells that have antiviral genes epigenetically silenced by DNA hypermethylation. Our results demonstrate that understanding the mechanism through which subclones of Huh-7 cells become permissive for HCV replication is crucial for studying their interaction with HCV.

AB - Hepatitis C virus (HCV) does not replicate efficiently in wild-type human hepatoma Huh-7 cells, but it replicates robustly in certain subclones of Huh-7 cells. Previously, we demonstrated that silencing of cyclic AMP (cAMP) response element binding protein 3-like 1 (CREB3L1), a cellular transcription factor that inhibits HCV replication, allows HCV to replicate in HRP1 cells, a subclone of Huh-7 cells permissive for HCV replication. Here we show that silencing of myxovirus resistant 1 (MX1), a known interferon-induced antiviral gene, is responsible for HRP4 cells, another subclone of Huh-7 cells, being permissive for HCV replication. Both CREB3L1 and MX1 are epigenetically silenced through DNA methylation in HRP1 and HRP4 cells, respectively. We further demonstrate that Huh-7 cells exist as a mixed population of cells with distinct patterns of gene methylation and HCV replicates in subpopulations of Huh-7 cells that have antiviral genes epigenetically silenced by DNA hypermethylation. Our results demonstrate that understanding the mechanism through which subclones of Huh-7 cells become permissive for HCV replication is crucial for studying their interaction with HCV.

UR - http://www.scopus.com/inward/record.url?scp=84871946952&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871946952&partnerID=8YFLogxK

U2 - 10.1128/JVI.01984-12

DO - 10.1128/JVI.01984-12

M3 - Article

VL - 87

SP - 659

EP - 665

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 1

ER -