Hepatitis C virus NS2/3 protease regulates HCV IRES-dependent translation and NS5B RdRp activity.
Chronic hepatitis C virus (HCV) infection often leads to liver cancer. NS2/3 protease is the first of two virally encoded proteases required for HCV polyprotein processing. In this report, we investigated the function of NS2/3 protease on HCV replication and translation. Cells transfected with plasmids encoding wild-type or mutant NS2/3 and a dual-luciferase reporter construct containing an HCV internal ribosome entry site (IRES) were used to examine the effect of NS2/3 protease on translation of HCV RNA. Cells transfected with plasmids encoding wild-type or mutant NS2/3, pcDNA-NS5B and a reporter plasmid were used to examine the effect of NS2/3 protease on HCV replication. The results showed that both autocleavage processing and the uncleaved form of NS2/3 protease specifically decrease HCV IRES-directed translation, while the uncleaved form of NS2/3 protease decreases HCV NS5B RdRp activity (replication), indicating that autoregulation by NS2/3 protease of HCV replication and translation may play an important role in persistent HCV infection.
She
Yinglong
Y
State Key Laboratory of Virology, College of Life Science, Wuhan Univerisity, 430072, Wuhan, Hubei, Poeple's Republic of China. swani@tom.com
Han
Tao
T
Ye
Linbai
L
Wu
Zhenghui
Z
D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D016174:Hepacivirus / Q000201:enzymology*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D046188:Protein Modification, Translational; D012367:RNA, Viral / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication
D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; D003546:Cysteine Endopeptidases; C107824:NS2-3 protease