Hepatitis C virus (HCV) NS2 protein up-regulates HCV IRES-dependent translation and down-regulates NS5B RdRp activity.

State Key Laboratory of Virology, College of Life Science, Wuhan Univerisity, 430072, Wuhan, Hubei, People's Republic of China.
Archives of Virology (Impact Factor: 2.28). 11/2008; 153(11):1991-7. DOI: 10.1007/s00705-008-0198-3
Source: PubMed

ABSTRACT 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.

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