| Hepatitis C virus (HCV) is identified the genus Hepacivirus within the family Flaviviridae. As many as 170 million individuals are infected with HCV worldwide. Although infected individuals exhibit mild symptoms during the acute phase of disease, HCV infection is characterized by a high rate of progression to metabolic disorders, steatosis, fibrosis, and chronic hepatitis, which can lead to cirrhosis and ultimately to hepatocellular carcinoma.HCV nonstructural protein 5B (NS5B) functions as an RNA-dependent RNA polymerase in the HCV replication complex derived from the endoplasmic reticulum in hepatic cells. CYP4F12 is a member of human cytochrome P450 (CYP450)family 4subfamily F, a group of fatty acids w-hydroxylase, which is rarely reported on function. In this study, NS5B was selected as bait in a yeast two-hybrid assay to screen a human liver cDNA library. We confirmed that CYP4F12 interacted with NS5B. Furthermore, overexpression of CYP4F12 facilitated HCV replication. In contrast, knockdown of CYP4F12 by specific shRNA decreased HCV replication and viral protein expression. Moreover, our results demonstrated that HCV infection increased the binding of the transcription factor SREBP1 to the CYP4F12 promoter and activated the promoter activity, which indicated that HCV infection increased the expression of CYP4F12, andin additional CYP4F11, through the SREBP1 pathway. Our results showed that HCV infection induced expression of CYP4F12 protein, which bound to the HCV replication complex to facilitate viral replication, and may shed new light on thepathological progression of HCV in the liver.. |
