TY - JOUR
T1 - Comparison of HCV-associated gene expression and cell signaling pathways in cells with or without HCV replicon and in replicon-cured cells
AU - Nishimura-Sakurai, Yuki
AU - Sakamoto, Naoya
AU - Mogushi, Kaoru
AU - Nagaie, Satoshi
AU - Nakagawa, Mina
AU - Itsui, Yasuhiro
AU - Tasaka-Fujita, Megumi
AU - Onuki-Karakama, Yuko
AU - Suda, Goki
AU - Mishima, Kako
AU - Yamamoto, MacHi
AU - Ueyama, Mayumi
AU - Funaoka, Yusuke
AU - Watanabe, Takako
AU - Azuma, Seishin
AU - Sekine-Osajima, Yuko
AU - Kakinuma, Sei
AU - Tsuchiya, Kiichiro
AU - Enomoto, Nobuyuki
AU - Tanaka, Hiroshi
AU - Watanabe, Mamoru
N1 - Funding Information:
This study was supported by grants from Ministry of Education, Culture, Sports, Science and Technology-Japan, the Japan Society for the Promotion of Science, Ministry of Health, Labour and Welfare-Japan, Japan Health Sciences Foundation, and National Institute of Biomedical Innovation.
PY - 2010/5
Y1 - 2010/5
N2 - Background: Hepatitis C virus (HCV) replication is affected by several host factors. Here, we screened host genes and molecular pathways that are involved in HCV replication by comprehensive analyses using two genotypes of HCV replicon-expressing cells, their cured cells and naïve Huh7 cells. Methods: Huh7 cell lines that stably expressed HCV genotype 1b or 2a replicon were used. The cured cells were established by treating HCV replicon cells with interferon-alpha. Expression of 54,675 cellular genes was analyzed by GeneChip DNA microarray. The data were analyzed by using the KEGG Pathway database. Results: Hierarchical clustering analysis showed that the gene-expression profiles of each cell group constituted clear clusters of naïve, HCV replicon-expressed, and cured cell lines. The pathway process analysis between the replicon-expressing and the cured cell lines identified significantly altered pathways, including MAPK, steroid biosynthesis and TGF-beta signaling pathways, suggesting that these pathways were affected directly by HCV replication. Comparison of cured and naïve Huh7 cells identified pathways, including steroid biosynthesis and sphingolipid metabolism, suggesting that these pathways were required for efficient HCV replication. Cytoplasmic lipid droplets were obviously increased in replicon-expressing and cured cells as compared to naïve cells. HCV replication was significantly suppressed by peroxisome proliferator-activated receptor (PPAR)-alpha agonists but augmented by PPAR-gamma agonists. Conclusion: Comprehensive gene expression and pathway analyses show that lipid biosynthesis pathways are crucial to support proficient virus replication. These metabolic pathways could constitute novel antiviral targets against HCV.
AB - Background: Hepatitis C virus (HCV) replication is affected by several host factors. Here, we screened host genes and molecular pathways that are involved in HCV replication by comprehensive analyses using two genotypes of HCV replicon-expressing cells, their cured cells and naïve Huh7 cells. Methods: Huh7 cell lines that stably expressed HCV genotype 1b or 2a replicon were used. The cured cells were established by treating HCV replicon cells with interferon-alpha. Expression of 54,675 cellular genes was analyzed by GeneChip DNA microarray. The data were analyzed by using the KEGG Pathway database. Results: Hierarchical clustering analysis showed that the gene-expression profiles of each cell group constituted clear clusters of naïve, HCV replicon-expressed, and cured cell lines. The pathway process analysis between the replicon-expressing and the cured cell lines identified significantly altered pathways, including MAPK, steroid biosynthesis and TGF-beta signaling pathways, suggesting that these pathways were affected directly by HCV replication. Comparison of cured and naïve Huh7 cells identified pathways, including steroid biosynthesis and sphingolipid metabolism, suggesting that these pathways were required for efficient HCV replication. Cytoplasmic lipid droplets were obviously increased in replicon-expressing and cured cells as compared to naïve cells. HCV replication was significantly suppressed by peroxisome proliferator-activated receptor (PPAR)-alpha agonists but augmented by PPAR-gamma agonists. Conclusion: Comprehensive gene expression and pathway analyses show that lipid biosynthesis pathways are crucial to support proficient virus replication. These metabolic pathways could constitute novel antiviral targets against HCV.
KW - DNA microarray
KW - HCV replicon
KW - KEGG database
KW - Lipid metabolism
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U2 - 10.1007/s00535-009-0162-3
DO - 10.1007/s00535-009-0162-3
M3 - Article
C2 - 20012654
AN - SCOPUS:77953323499
VL - 45
SP - 523
EP - 536
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
SN - 0944-1174
IS - 5
ER -