Scientific Online Resource System

Biomedical Reviews

Hepatitis C virus translation and cell cycle

Masao Honda


The 5' nontranslated region (NTR) of hepatitis C virus (HCV) contains highly structured segments which form internal ribosome entry site (IRES). This cis-active RNA element direct the cap-independent initiation of translation of the viral polyprotein in association with trans-acting cellular proteins. Thus HCV IRES plays a key role in the replication of virus, especially in liver in which various cellular proteins changes in their expression levels under the condition of chronic hepatitis. To construct a system in which HCV IRES activity could be continuously monitored in vivo, 2 stably transformed cell lines from Huh-7 cells (human hepatocellular carcinoma cells) that express a reporter protein (firefly luciferase) under the translational control of the IRES were established. The activity of the HCV IRES varies in different phases of the cell cycle and HCV IRES activity is highest during the mitotic (G2/M) phases of the cell cycle and lower in the quiescent (G0) phases. The gene expression dynamics of host factors and kinetics of HCV IRES activity in cells at various points during the cell cycle were evaluated using a cDNA microarray. HCV TRES activity correlated with a gene cluster induced in S and G2/M phases. Interestingly, most initiation factors known to bind or interact with HCV IRES (PCBP2, PTB, eIF3, eIF2 gamma, eIF2 beta, La protein and RNLPL) were induced during S and G2/M phases. Of these factors, the expression of La protein, PTB and eIF3 (p116, 170) were predominantly repressed in quiescent (G0) and induced in S and G2/M phases. Suppression or overexpression of La protein and PTB in cells significantly changed HCV IRES activity. In the livers of patients with chronic hepatitis C, the expression of La protein was significantly increased and correlated with the amount of HCV-RNA. Collectively, these data indicated that HCV utilizes host factors induced during cell division but not during quiescence for replication. Of these, La protein is a potent regulator and enhances HCV replication in regenerating hepatocytes in patients with chronic hepatitis C.

Biomedical Reviews 2004; 15: 37-46.

Full Text



Article Tools
Email this article (Login required)
About The Author

Masao Honda
Kanazawa University

Font Size