Activation of refractory T cell responses against hepatitis C virus core protein by ablation of interfering hydrophobic domains

Helen A. Andersson, Rana A.K. Singh, Michael A. Barry

Research output: Contribution to journalArticle

3 Scopus citations

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 languageEnglish (US)
Pages (from-to)338-346
Number of pages9
JournalMolecular Therapy
Volume13
Issue number2
DOIs
StatePublished - Feb 1 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

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