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.
Original language | English (US) |
---|---|
Pages (from-to) | 338-346 |
Number of pages | 9 |
Journal | Molecular Therapy |
Volume | 13 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2006 |
Keywords
- Cellular immunity
- Core protein
- Genetic immunization
- HCV
- Hydrophobicity
- Proteasome
- Ubiquitin
- Vaccine
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
- Pharmacology
- Drug Discovery