FIG. 17.
Translational control by HCV. (A) Structural representation of the HCV polyprotein. The individual positions of the polyprotein cleavage products are shown. NS5A (black region) from IFN-resistant HCV can bind and repress PKR (129, 133). (B) NS5A blocks PKR-dependent eIF2α phosphorylation. eIF2α phosphorylation from control (Neo) NIH 3T3 cell lines and those stably expressing NS5A from IFN-resistant HCV (NS5A-1A) or a nonfunctional NS5A mutant (ΔISDR) was assessed by single-dimension isoelectric focusing of cell extracts and anti-eIF2α immunoblot analysis (133). Cells were mock infected (lanes 1, 3, and 5) or infected with VSV (lanes 2, 4, and 6). Arrows denote the positions hypo- and hyper-phosphorylated isoforms of eIF2α (eIF2α and eIF2αP, respectively). Hyperphosphorylated eIF2α is phosphorylated on serine 51 by PKR and is sufficient to block mRNA translation (61, 89).