Inducible CYP4F12 enhances Hepatitis C virus infection via association with viral nonstructural protein 5B

• Published in: Biochemical and biophysical research communications 2016-02, Vol.471 (1), p.95-102
• Main Authors: Zhu, Sheng-Li, Wang, Li, Cao, Zhong-Ying, Wang, Jun, Jing, Ming-Zhen, Xia, Zhang-Chuan, Ao, Fang, Ye, Lin-Bai, Liu, Shi, Zhu, Ying
• Format: Article
• Language: English
• Subjects: Aryl Hydrocarbon Hydroxylases - metabolism; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - virology; cDNA libraries; Cell Line, Tumor; complementary DNA; CYP4F12; cytochrome P-450; endoplasmic reticulum; Hepacivirus - physiology; Hepatitis C - metabolism; Hepatitis C - virology; Hepatitis C virus; Humans; liver; protein synthesis; RNA-directed RNA polymerase; transcription factors; two hybrid system techniques; viral nonstructural proteins; Viral Nonstructural Proteins - metabolism; Viral replication; virus replication; Virus Replication - physiology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.01.173

Hepatitis C virus (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. In this study, NS5B was used as bait in a yeast two-hybrid assay to screen a human liver cDNA library. We confirmed that CYP4F12, a member of the cytochrome P450 superfamily, 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 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. •HCV infection induces CYP4F12 expression.•NF-κB/P50 and SREBP1 are involved in the induction of CYP4F12 expression.•CYP4F12 interacts with HCV NS5B, leading to the enhancement of HCV replication.