Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma.
Steatosis is an established risk factor for disease progression in cases of chronic hepatitis C. Recently it was demonstrated that Hepatitis C virus (HCV) core and non-structural (NS) 2 proteins (NS2) induce lipid accumulation in hepatic cells. However, it has yet to be determined whether other HCV proteins are associated with lipid metabolism. The NS5A augmented the transcriptional activity and gene expression of PPARgamma. Furthermore, NS5A increased the ability to recruit the transcriptional coactivator PGC-1s to the PPRE with PPARgamma, as well as the interaction with PPARgamma2 and PGC-1alpha. Our results indicate that NS5A may exploit multiple strategies that enhance PPARgamma-induced lipid accumulation.
Kim
Kyeongjin
K
Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
Kim
Kook Hwan
KH
Ha
Eunsin
E
Park
Jin Young
JY
Sakamoto
Naoya
N
Cheong
Jaehun
J
D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034622:RNA Interference; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
D006360:Heat-Shock Proteins; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014157:Transcription Factors; D017361:Viral Nonstructural Proteins; C486497:PPARGC1A protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C039671:ciglitazone