The polypyrimidine tract-binding protein (PTB) is required for efficient replication of hepatitis C virus (HCV) RNA

Our earlier work found that the polypyrimidine tract-binding protein (PTB) specifically interacts with the poly(U/C) tract of the hepatitis C virus (HCV) 3' untranslated region (3'UTR) [Luo, G., 1999. Cellular proteins bind to the poly(U) tract of the 3' untranslated region of hepatitis C virus RNA genome. Virology 256, 105-118]. We report here that the phosphorylated form of PTB is associated with the membrane-bound HCV replication complex. To determine whether the PTB is required for HCV RNA replication, synthetic small interfering RNAs (siRNAs) were used to specifically knockdown PTB expression in the HCV replicon-harboring Huh7 cells. The level of PTB expression was efficiently reduced by PTB-specific siRNAs. Consequently, the levels of HCV proteins as well as HCV RNA were proportionally decreased by increasing concentrations of PTB siRNA. However, the translation mediated by the encephamyocarditis virus internal ribosome entry site was unaffected, suggesting that the inhibition of HCV RNA replication by PTB siRNA was not due to its effect on the EMCV IRES-mediated translation. Collectively, these findings demonstrate that PTB is required for efficient HCV RNA replication in the cell.