GCN5 Acetyltransferase Inhibits PGC1α-induced Hepatitis B Virus Biosynthesis

作     者：Xiaohui Tian Fei Zhao Zhikui Cheng Ming Zhou Xiaoguang Zhi Jiafu Li Kanghong Hu 

作者机构：State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences Department of Obstetrics and Gynecology Zhongnan Hospital of Wuhan University Biomedical Center Hubei University of Technology 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2013年第28卷第4期

页      面：216-222页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：supported by grants from the National Major Science and Technology Special Projects for Infectious Diseases of China (2012ZX10004503-008  2012ZX10001006-002 and 2012ZX10002006-002) 

主　　题：Hepatitis B Virus (HBV) PGClα GCN5 Acetylation 

摘      要：Hepatitis B virus （HBV） biosynthesis is primarily restricted to hepatocytes due to the governing of liver-enriched nuclear receptors （NRs） on viral RNA synthesis. The liver-enriched NR hepatocyte nuclear factor 4α （HNF4α, the key regulator of genes implicated in hepatic glucose metabolism, is also a primary determinant of HBV pregenomic RNA synthesis and HBV replication. Peroxisome proliferator-activated receptor-r coactivator la （PGCla） coactivates and further enhances the effect of HNF4α on HBV biosynthesis. Here, we showed that the acetyltransferase General Control Non-repressed Protein 5 （GCN5） acetylated PGC 1 α, leading to alteration of PGC 1 α from a transcriptionally active state into an inactive state. As a result, the coactivation activity of PGCla on HBV transcription and replication was suppressed. Apparently, an acetylation site mutant of PGC 1 α （PGC 1 αR13） still had coactivation activity as GCN5 could not suppress the coactivation activity of the mutant. Moreover, a catalytically inactive acetyltransferase mutant GCN5m, due to the loss of acetylation activity, failed to inhibit the coactivation function of PGClα in HBV biosynthesis. Our results demonstrate that GCN5, through its acetyltransferase activity, inhibits PGCla-induced enhancement of HBV transcription and replication both in vitro and in vivo.