Hepatitis C virus (HCV) is a positive-stranded RNA virus classified in the Hepacivirus genus in the family Flaviviridae. The 9.6-kb viral RNA genome encodes a precursor polyprotein that is processed to generate at least 10 viral proteins, including structural proteins (core, E1, E2, and p7) and nonstructural proteins (NS2, NS3, NS4A, NS4B, NS5A, and NS5B) (1). The NS5B RNA polymerase, together with other nonstructural viral proteins (NS3, NS4A, NS4B, and NS5A) and host factors, constitutes the active replication complexes (RC) for viral RNA replication. These proteins are directly or indirectly associated with the endoplasmic reticulum (ER)-derived structure called the "membranous web," where replication occurs (2, 3). However, the exact host factors and detailed interactions within the RC remain to be determined.HCV infection usually causes chronic hepatitis and frequently leads to cirrhosis and hepatocellular carcinoma (HCC). Besides, HCV-induced end-stage liver disease is an important indication for liver transplantation in most of the Western countries (4, 5). At present, no effective vaccine to prevent HCV infection is available. The current treatment strategies for HCV infection are valid only for individuals with a particular single nucleotide polymorphism (SNP) in the interleukin-28B gene or for infections caused by certain viral genotypes (6). Accordingly, the prevalence of hepatic steatosis in HCV-infected patients is much higher than that in the general population or in hepatitis B virus (HBV)-infected patients (7). Hepatic steatosis has also been reported to be associated with an increased rate of HCC in chronic hepatitis C patients (8).Lipid metabolic pathways are essential for the entry, secretion, and replication of HCV. For example, apolipoprotein E (apoE) is essential for the production of HCVcc (HCV produced in cell culture) and for viral entry (9, 10). Downregulation of apoA-I decreases levels of HCV replication and viral particle production in cell culture (11). HCV coopts the secretory pathway of very low density lipoprotein (VLDL) for its own secretion (12, 13). Moreover, HCV replication is regulated through induction of lipogenic gene expression in HCV replicon cells (14) or geranylgeranylation of host proteins required for HCV RNA replication (15,16). Fatty acid synthesis is also required for HCV RNA replication (14). Inhibition of fatty acid synthase (FASN) by cerulenin (17) or C75 (18) reduces the replication of subgenomic HCV replicons as well as JFH-1-based HCVcc virion production. Although the underlying mechanisms are not yet completely understood, these studies imply that FASN is essential for HCV replication.In this study, HCV NS5B was used as the bait to screen for NS5B-interacting proteins that are present in Huh7 hepatoma cell lysates. After mass spectrophotometric analysis, FASN was found to interact with NS5B, and this interaction was further confirmed in vitro and in vivo. Our data indicate that FASN interacts with NS5B to enhance NS5B RNA-dependent RNA polymerase (RdRp) act...

The Chinese herb modified Yi Guan Jian (mYGJ) is an effective regimen that is usually used in outpatients with chronic liver diseases such as fibrosis and cirrhosis. However, the mechanism for the action of mYGJ on liver fibrosis is not yet clear. In this study, we found that mYGJ induced hepatic stellate cells (HSCs) apoptosis concomitant with the downregulation of Bcl-2 expression and slight elevation of Bax level. Moreover, the reactive oxygen species (ROS) were generated in the early stages of mYGJ-induced HSCs apoptosis to facilitate calcium and cytochrome c release from the mitochondria to cytosol. Subsequently, caspase 9 and caspase 3 were activated. Furthermore, the activation of ER stress-associated caspase 12 in HSCs was also evaluated. Together, we report the first evidence-based study to demonstrate that mYGJ decoction induces HSCs apoptosis through ROS accumulation and the intrinsic apoptosis pathway. These findings provide rationale for further clinical investigation of traditional Chinese medicine recipes against liver fibrosis.