Hepatitis C virus (HCV) NS2 protein up-regulates HCV IRES-dependent translation and down-regulates NS5B RdRp activity.
Chronic hepatitis C virus (HCV) infection often leads to liver cancer. The HCV NS2 protein is a hydrophobic transmembrane protein that associates with several cellular proteins in mammalian cells. In this report, we investigated the function of NS2 protein on HCV replication and translation by using a transient cell-based expression system. Cells co-transfected with pcDNA3.1 (-)-NS2 and the dual-luciferase reporter construct containing the HCV IRES were used to detect the effect of NS2 protein on HCV translation. Cells co-transfected with pcDNA3.1(-)-NS2, pcDNA-NS5B and a reporter plasmid were used to detect the effect of NS2 protein on HCV replication. The results showed that HCV NS2 protein up-regulated HCV IRES-dependent translation in a specific and dose-dependent manner in Huh7 cells but not in HeLa and HepG2 cells, and NS2 protein inhibited NS5B RdRp activity in a dose-independent manner in all three cell lines. These findings may suggest a novel mechanism by which HCV modulates its NS5B replication and IRES-dependent translation and facilitates virus persistence.
State Key Laboratory of Virology, College of Life Science, Wuhan Univerisity, 430072, Wuhan, Hubei, People's Republic of China.
Yinglong
Y
She
Qingjiao
Q
Liao
Xulin
X
Chen
Linbai
L
Ye
Zhenghui
Z
Wu
D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D014176:Protein Biosynthesis; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
C097010:NS2 protein, Hepatitis C virus; D017361:Viral Nonstructural Proteins; D012324:RNA-Dependent RNA Polymerase