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  • Title: Activation of refractory T cell responses against hepatitis C virus core protein by ablation of interfering hydrophobic domains.
    Author: Andersson HA, Singh RA, Barry MA.
    Journal: Mol Ther; 2006 Feb; 13(2):338-46. PubMed ID: 16242998.
    Abstract:
    Hepatitis C virus (HCV) is the major pathogen of chronic hepatitis and liver disease, but currently there are no prophylactic HCV vaccines available. The HCV core protein-encoding sequence is among the most conserved genes in the HCV genome, making it a prime candidate for a component of a vaccine. The core protein localizes to the endoplasmic reticulum (ER) through a C-terminal hydrophobic region that is cotranslationally inserted into the ER membrane. Here we show that removal of the C-terminal hydrophobic region confers nuclear localization and enhances proteasomal degradation of the core protein in mammalian cells. This efficient protein proteolysis induces enhanced core-specific CD8(+) T cell responses in BALB/c mice immunized with plasmids expressing C-terminal deletions of the HCV core protein. These results suggest that more potent HCV vaccines can be achieved by targeting the core protein for proteasomal degradation by deletion of its C-terminal hydrophobic domain.
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