GIBH Scientists Found the Important Role of Hepatocyte Nuclear Factor 4α (HNF4α) in the Regulation of Assembly and Secretion of Hepatitis C Virus

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. The assembly and secretion of HCV are closely correlated with the very-low-density lipoprotein (VLDL) secretory pathway. However, the molecular mechanism by which HCV cooperates with VLDL to facilitate assembly and release is unclear.  

Recently, Dr. Tao Peng’ research group in GIBH cooperated with Dr. Ling Chen reported the function of hepatocyte nuclear factor 4α (HNF4α), the most abundant liver-enriched transcription factor, in HCV assembly and release. HNF4αis crucial in VLDL-mediated lipid transport. They found that HNF4α antagonist or knockdown impaired HCV assembly and secretion, while ectopic expression of HNF4α promoted infectious HCV production. They also identified a novel factor, phospholipase A₂ GXIIB (PLA₂GXIIB) involved in VLDL secretion, was required for HCV secretion. The two HNF4α-controlled factors, PLA₂GXIIB and microsomal triglyceride transfer protein, were contributed to the regulation of HCV infectivity induced by HNF4α. This study emphasizes the importance of the VLDL secretory pathway for HCV assembly and secretion, and provides insights into the mechanism by which HCV cooperates with HNF4αto be assembled into and released together with VLDL particles. The results have been published online in the Journal of Virology (http://jvi.asm.org/content/early/2013/10/24/JVI.02068-13.abstract).