TY - JOUR
T1 - Epigenetic silencing of interferon-inducible genes is implicated in interferon resistance of hepatitis C virus replicon-harboring cells
AU - Naka, Kazuhito
AU - Abe, Ken ichi
AU - Takemoto, Kazunori
AU - Dansako, Hiromichi
AU - Ikeda, Masanori
AU - Shimotohno, Kunitada
AU - Kato, Nobuyuki
N1 - Funding Information:
We would like to thank T. Nakamura, T. Maeta, and A. Morishita for their helpful assistance with the experiments. This work was supported by grants-in-aid for a third-term comprehensive 10-year strategy for cancer control, and for research on hepatitis from the Ministry of Health, Labor, and Welfare of Japan, as well as by the program for the promotion of fundamental studies in Health Sciences of the Pharmaceutical and Medical Devices Agency (PMDA).
PY - 2006/5
Y1 - 2006/5
N2 - Background/Aims: We previously established hepatitis C virus (HCV) replicon-harboring cell lines possessing two interferon (IFN)-resistant phenotypes: a partially resistant phenotype (αR series) and a severely resistant phenotype (βR series). We recently found that the severe IFN resistance of the βR-series cells is caused by the functional disruption of type I IFN receptors. Here, we aimed to clarify the mechanism(s) underlying the partial IFN resistance of the αR-series cells. Methods: αR-series cells were pre-treated with 5-azacytidine to evaluate the effects of DNA demethylation on IFN resistance. cDNA microarray analysis was carried out in order to compare 1αR cells, which belong to the αR series, treated with both 5-azacytidine and IFN-α with cells treated with 5-azacytidine or IFN-α alone. Results: We found that the IFN-resistant phenotype of αR-series cells was impaired by treatment with 5-azacytidine. cDNA microarray analysis identified seven IFN-stimulated genes, which were up-regulated by 5-azacytidine treatment. We demonstrated here that the ectopic expression of each of these seven genes in 1αR cells frequently weakened the IFN resistance of these cells. Conclusions: The present results suggest that the epigenetic silencing of IFN-stimulated genes is implicated in the acquisition of a partially IFN-resistant phenotype of HCV replicon-harboring cells.
AB - Background/Aims: We previously established hepatitis C virus (HCV) replicon-harboring cell lines possessing two interferon (IFN)-resistant phenotypes: a partially resistant phenotype (αR series) and a severely resistant phenotype (βR series). We recently found that the severe IFN resistance of the βR-series cells is caused by the functional disruption of type I IFN receptors. Here, we aimed to clarify the mechanism(s) underlying the partial IFN resistance of the αR-series cells. Methods: αR-series cells were pre-treated with 5-azacytidine to evaluate the effects of DNA demethylation on IFN resistance. cDNA microarray analysis was carried out in order to compare 1αR cells, which belong to the αR series, treated with both 5-azacytidine and IFN-α with cells treated with 5-azacytidine or IFN-α alone. Results: We found that the IFN-resistant phenotype of αR-series cells was impaired by treatment with 5-azacytidine. cDNA microarray analysis identified seven IFN-stimulated genes, which were up-regulated by 5-azacytidine treatment. We demonstrated here that the ectopic expression of each of these seven genes in 1αR cells frequently weakened the IFN resistance of these cells. Conclusions: The present results suggest that the epigenetic silencing of IFN-stimulated genes is implicated in the acquisition of a partially IFN-resistant phenotype of HCV replicon-harboring cells.
KW - DNA methylation
KW - Epigenetic silencing
KW - HCV replicon
KW - IFN resistance
KW - cDNA microarray
UR - http://www.scopus.com/inward/record.url?scp=33645797382&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645797382&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2006.01.030
DO - 10.1016/j.jhep.2006.01.030
M3 - Article
C2 - 16545484
AN - SCOPUS:33645797382
SN - 0168-8278
VL - 44
SP - 869
EP - 878
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 5
ER -
